• Autonomic function
• constipation
• postoperative recovery
• thoracolumbar vertebral fracture
• transcutaneous electrical acustimulation

• Anxiety
• Colon
• Compulsion
• Hemorrhagic shock and resuscitation
• Hydrogen sulfide

• Animals
• Receptors, N-Methyl-D-Aspartate/metabolism
• Hydrogen Sulfide
• Shock, Hemorrhagic/drug therapy
• Shock, Hemorrhagic/metabolism
• Shock, Hemorrhagic/therapy
• Male
• Disease Models, Animal
• Anxiety/drug therapy
• Mice
• Colon/pathology
• Colon/drug effects
• Resuscitation
• Alkynes/therapeutic use
• Alkynes/pharmacology
• Mice, Inbred C57BL
• Glycine/analogs & derivatives
• Behavior, Animal/drug effects
• Amygdala/metabolism
• Amygdala/drug effects

• Acute pancreatitis
• Autonomic nervous function
• Gastrointestinal hormone
• Gastrointestinal motility
• Transcutaneous gastric pacing

• Humans
• Gastrointestinal Motility
• Male
• Female
• Vasoactive Intestinal Peptide/blood
• Middle Aged
• Pancreatitis/therapy
• Pancreatitis/physiopathology
• Pancreatitis/blood
• Adult
• Ghrelin/blood
• Heart Rate
• Acute Disease
• Stomach/innervation
• Stomach/physiopathology
• Transcutaneous Electric Nerve Stimulation/methods
• Interleukin-6/blood
• Treatment Outcome
• Aged

• YK202043 the Scientific Research Project of Suzhou Ninth People's Hospital
• SKYXD2022041 the Science and Technology Development Program of Suzhou
• the Scientific Research Project of Suzhou Ninth People’s Hospital

• Electroacupuncture
• PC6
• Postoperative gastrointestinal recovery
• Postoperative ileus
• ST36

• Electroacupuncture
• Gut microbiota
• Microbiome-gut-brain axis
• Neuroinflammation
• Perioperative neurocognitive disorder

• Animals
• Electroacupuncture/methods
• Gastrointestinal Microbiome/physiology
• Male
• Mice
• Hippocampus/metabolism
• Mice, Inbred C57BL
• Brain-Gut Axis/physiology
• Fecal Microbiota Transplantation
• Disease Models, Animal
• Neurocognitive Disorders/therapy
• Neurocognitive Disorders/metabolism
• Neuroinflammatory Diseases/metabolism
• Memory
• Cognition

• acupuncture
• gastrointestinal disease
• gut microbiota
• mental disorders
• metabolic disease
• nervous system disease

• Gastrointestinal Microbiome
• Humans
• Acupuncture Therapy
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Diseases/therapy
• Mental Disorders/therapy
• Mental Disorders/microbiology
• Nervous System Diseases/therapy
• Nervous System Diseases/microbiology
• Animals
• Metabolic Diseases/microbiology
• Metabolic Diseases/therapy

• autonomic nervous system
• dysmenorrhea
• electroacupuncture
• laser acupuncture
• prostaglandins
• quality of life

• Humans
• Female
• Dysmenorrhea/therapy
• Dysmenorrhea/physiopathology
• Electroacupuncture/methods
• Cross-Over Studies
• Adult
• Autonomic Nervous System/physiopathology
• Heart Rate/physiology
• Quality of Life
• Young Adult
• Acupuncture Therapy/methods
• Prostaglandins
• Acupuncture Points
• Treatment Outcome

• Alzheimer’s disease
• acupuncture
• gut microbiota
• inflammation
• probiotics

• acupuncture
• autonomic nervous system
• neuronal circuit
• parasympathetic nerve
• sympathetic nerve

• depressive disorder
• gut microbiota
• gut permeability
• microbiota-gut-brain axis
• vagus nerve

Previous fundamental and clinical research has shown that electroacupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) can successfully alleviate motor dysfunction following stroke. Additionally, it has been discovered that gut microbiota and their metabolites play an essential role in stroke. However, the relationship between the metabolites of gut microbiota and the efficacy of EA is still unclear. Therefore, the aim of this study was to evaluate the mechanism of EA at LI11 and ST36 in the treatment of motor dysfunction after middle cerebral artery occlusion/reperfusion (MCAO/R) in model rats by comparing the differences and correlation between different short-chain fatty acids (SCFAs) and the recovery of motor function. The results indicated that EA at LI11 and ST36 acupoints enhanced the neurological function, motor function, and infarct volume of MCAO/R rats. The levels of acetic acid, propionic acid, and total SCFAs were considerably lower in the MCAO/R group than in the sham group (P < 0.05). Acetic acid, propionic acid, and total SCFA concentrations were substantially higher in the MCAO/R + EA group than in the MCAO/R group (P < 0.05). Finally, Pearson correlation analysis revealed that the propionic acid concentration was substantially favorably connected with the duration on the rotarod (r = 0.633 and P < 0.05) and highly negatively correlated with the modified neurological severity score (mNSS) (r = −0.698 and P < 0.05) and the percentage of cerebral infarct volume (r = −0.729 and P < 0.05). Taken together, these findings indicate that the increase in propionic acid may be one of the mechanisms and targets of EA at LI11 and ST36 acupoints to improve poststroke motor dysfunction in MCAO/R rats.

Electroacupuncture (EA) at the Zusanli acupoint (ST36) has shown therapeutic potential for sepsis due to its ability to limit inflammation and to regulate gastrointestinal tract symptoms. However, the mechanisms contributing to the effects of EA at ST36 on sepsis and connections with the intestinal flora remain unclear. This study was designed to explore the effects of EA at ST36 on Toll-like receptor 4 signaling and the intestinal flora.

ICR mice were randomly divided into 4 groups: control group, model group, EA group, and sham EA group. EA at ST36 was performed at 2.5 mA and 2 to 100 Hz, and the 30 min of dense wave was achieved over 5 days. A sepsis model was built by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/mL). The levels of expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and IL-10 were detected by enzyme-linked immunosorbent assays, and lactate dehydrogenase (LDH) levels in serum were measured by biochemical tests. Expression levels of Bax, Bcl2, cleaved caspase-3, Toll-like receptor (TLR4), nuclear factor-kappa B (NF-κB), and myeloid differentiation factor 88 (MyD88) were assessed by the Western blotting. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to evaluate apoptosis. The intestinal microecology was assessed via 16S rRNA gene sequencing.

EA at ST36 reduced the expression of IL-1β, IL-6, and TNF-α and increased the expression of IL-10 to inhibit the inflammatory response. EA at ST36 also inhibited apoptosis, as measured by TUNEL staining, and decreased the Bax/Bcl2 ratio and levels of caspase-3 and cleaved caspase-3, as well as LDH release. Our results suggest that alleviation of sepsis may correlate with the downregulation of levels of TLR4, NF-κB, and MyD88. Importantly, EA at ST36 improved the diversity of the intestinal flora and increased the abundance of Firmicutes and Actinobacteria. Conclusion. EA at ST36 prevented sepsis from worsening by inhibiting inflammation and apoptosis, which correlated with the regulation of the TLR4/NF-κB/MyD88 signaling axis and modulation of the intestinal flora.

• acute pancreatitis
• analgesia
• gastrointestinal dysmotility
• inflammation
• transcutaneous electrical acustimulation

• BDL
• HO-1
• cholinergic anti-inflammatory pathway
• electroacupuncture
• αn7AChR

• Rats
• Mice
• Male
• Animals
• Electroacupuncture
• Interleukin-10
• Rats, Sprague-Dawley
• Occludin
• Neuroimmunomodulation
• alpha7 Nicotinic Acetylcholine Receptor
• Claudin-1
• Chemical and Drug Induced Liver Injury, Chronic
• Mice, Inbred C57BL
• Intestines
• Cholestasis
• Liver Cirrhosis
• Bile Ducts/surgery

So far, a number of acupuncture studies have shown anti-inflammatory effects of acupuncture treatment, mostly known at specific point ST36. However, there is no literature that oversaw the inflammation-regulatory effects of acupuncture in each tissue. Therefore, we investigated how acupuncture at specific acupoint ST36 regulates inflammation and its underlying mechanisms. We searched literatures on PubMed until July 2021 using the keywords “animal, acupuncture, ST36, inflammation, immune,” and 292 literatures were searched. We ultimately selected 69 studies to determine the anti-inflammatory actions of acupuncture at ST36 and classified the changes of inflammatory mediators according to target regions. Forty-three studies were included in body fluids, 27 studies in the digestive system, 17 studies in the nervous system, and 30 studies in other tissues or organs. In this review, we found that acupuncture at ST36 has clinical benefits in relieving inflammation through several mechanisms such as vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, mitogen-activated protein kinase (MAPK) signaling pathway, and cholinergic anti-inflammatory pathway. We expect that these data will inform further studies related to ST36 acupuncture on inflammation.

• acupoint ST36
• acupuncture
• animal study
• anti-inflammatory effects
• literature review

• abdominal distension
• abdominal pain
• acupuncture
• acute pancreatitis
• meta-analysis
• systematic review

• Analgesics, Opioid/pharmacology
• Brain-Gut Axis/drug effects
• Comorbidity
• Gastrointestinal Microbiome/drug effects
• Hemostasis/drug effects
• Humans
• Neuroinflammatory Diseases/chemically induced
• Neuroinflammatory Diseases/prevention & control

Background and Purpose: Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine (ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4β2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined.

Experimental Approach: In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured.

Results: Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment.

Conclusion and Implications: Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.

• cholinergic transmission
• cytisine
• neuroprotection
• synaptic remodeling
• temporal lobe epilepsy
• α7nAChRs

• Nrf2
• hemorrhagic shock-induced renal injury
• ophiopogonin A
• p-ERK/ERK
• renal injury

Acupuncture at Zusanli (ST36), Quchi (LI11), and Tianshu (ST25) is commonly used in septic patients by traditional Chinese physicians. The protective effect of acupuncture at ST36 on the intestinal barrier is associated with Cholinergic Anti-Inflammatory Pathway (CAIP). However, its detailed mechanism and whether acupuncture at LI11 and ST25 have similar effects to ST36 remain unclear.

To explore the effects of electroacupuncture (EA) at ST36, LI11, and ST25 on septic rats and investigate the role of the spleen in the treatment of EA at ST36.

A septic rat model caused by cecal ligation and puncture (CLP) and a postsplenectomy (SPX) CLP rat model were established. Rats were divided into nine groups depending on different treatments. Serum levels of TNF-α, IL-10, D-lactic acidosis (D-LA), double amine oxidase (DAO), and T-lymphocyte subgroup level in intestinal lymph nodes were compared.

EA could not improve the 2-day survival of CLP rats. For CLP rats, EA at ST36 and LI11 significantly decreased the levels of TNF-α, IL-10, DAO, and D-LA in serum and normalized intestinal T-cell immunity. For SPX CLP rats, EA at ST36 failed to reduce serum concentrations of TNF-α, IL-10, and D-LA but increased the values of CD3⁺CD4⁺/CD3⁺CD8⁺ cells and Treg/Th17 cells.

EA at ST36 and LI11, respectively, could alleviate inflammation reaction, protect the intestinal barrier, and maintain intestinal T-cell function in septic rats. Spleen participated in the protective effect of EA at ST36 in sepsis.

• Acupuncture
• Gut microbial dysbiosis
• Microbiome-gut-brain axis
• Neuroinflammation
• Parkinson’s disease

• Postoperative gastrointestinal function
• Protocol
• Randomized controlled trials
• TEAS

• Abdomen/surgery
• Adult
• Electroacupuncture/methods
• Gastrointestinal Diseases/therapy
• Humans
• Length of Stay
• Pain, Postoperative/therapy
• Postoperative Complications/therapy
• Prospective Studies
• Randomized Controlled Trials as Topic
• Recovery of Function
• Treatment Outcome

Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acupuncture has a benign adjustment effect on gastrointestinal (GI) movement; however, the mechanism of this effect is unclear, especially in terms of neural mechanisms, and there are still many areas that require further exploration. This article reviews the recent data on the neural mechanism of acupuncture on GI movements. We summarize the neural mechanism of acupuncture on GI movement from four aspects: acupuncture signal transmission, the sympathetic and parasympathetic nervous system, the enteric nervous system, and the central nervous system.

• Acupuncture
• Gastrointestinal motility
• Neuromechanism
• Afferent fibers
• Autonomic nervous system
• Central nervous system

• Acupuncture Therapy
• Animals
• China
• Enteric Nervous System
• Gastrointestinal Motility
• Gastrointestinal Tract/diagnostic imaging
• Humans

The relationship between inflammatory bowel disease and gut microbiota is inextricable. Electroacupuncture (EA) can alleviate acute experimental colitis, but the performance of intestinal microorganisms and the mechanism are still not fully understood. We investigated the relationship between the EA and gut microbes and clarified the role of tight junction and adiponectin in the anti-inflammatory effect of EA.

Male C57BL/6 mice were randomized into three groups: normal control, dextran sulfate sodium- (DSS-) induced ulcerative colitis (DSS), and DSS with EA ST36 (DSS + EA). Mice body weight, DAI score, colon length, and histological score were evaluated for colitis severity. Colonic inflammation and tight junctions were demonstrated by the immunohistochemical (IHC) method. Systemic responses were confirmed by plasma cytokines and adiponectin with multiplex immunoassays. Gut microbiome profiling was conducted by 16S rRNA gene sequencing.

EA had benefit in relieving both macroscopic and microscopic colonic inflammation. It can reduce disease activity, maintain colon length, and ameliorate histological inflammatory reaction. In IHC stain, EA decreased CD11b, F4/80, TLR4, and MyD88 and preserved claudin-1 and ZO-1 expression. Compared with the control group, the DSS group showed elevated levels of CRP, IFN-γ, TNF-α, and IL-6, but decreased adiponectin. These changes were reversed by EA, accompanied by modulation of the overall structure of gut microbiota.

Our findings suggest that EA exerts its therapeutic effect by TLR4 signaling via the MyD88-dependent pathway. EA could increase adiponectin, maintain mucosal tight junctions, and modulate gut microbiota.

Electroacupuncture (EA) at ST36 can improve the survival rate in rats after hemorrhagic shock (HS). The current study investigated rats with 60% blood loss. 144 rats were divided into four groups: hemorrhage without fluid resuscitation (HS), EA after hemorrhage without fluid resuscitation (EA), hemorrhage with delayed resuscitation (DFR), and EA after hemorrhage with delayed resuscitation (EA + DFR). The survival rate and biological parameters 0, 3, 12, and 24 h after HS were investigated. The 24 h survival rate of EA + DFR was significantly higher than that of DFR. 12 h after hemorrhage, the level of mean arterial blood pressure of EA + DFR was significantly higher than that of DFR, and the levels of renal blood flow, intestinal mucosal blood flow, and hepatic blood flow of EA + DFR were also significantly higher than those of DFR. Three hours after hemorrhage, the levels of lactate, PaCO₂, alanine aminotransferase, and creatinine of groups receiving EA were significantly lower than those of non-EA groups, and the levels of pH, PaO₂, and diamine oxidase of groups receiving EA were significantly higher. EA at ST36 can improve the 24 h survival rate and produce the experimental antishock effects on tissue perfusion and organ protection from fatal HS.

• Electroacupuncture
• Fibrosis
• Macrophage polarization
• Skeletal muscle contusion

Hemorrhagic shock (HS), a major cause of early death from trauma, accounts for around 40% of mortality, with 33–56% of these deaths occurring before the patient reaches a medical facility. Intravenous fluid therapy and blood transfusions are the cornerstone of treating HS. However, these options may not be available soon after the injury, resulting in death or a poorer quality of survival. Therefore, new strategies are needed to manage HS patients before they can receive definitive care. Recently, various forms of neuromodulation have been investigated as possible supplementary treatments for HS in the prehospital phase of care. Here, we provide an overview of neuromodulation methods that show promise to treat HS, such as vagus nerve stimulation, electroacupuncture, trigeminal nerve stimulation, and phrenic nerve stimulation and outline their possible mechanisms in the treatment of HS. Although all of these approaches are only validated in the preclinical models of HS and are yet to be translated to clinical settings, they clearly represent a paradigm shift in the way that this deadly condition is managed in the future.

• Autonomic nervous system
• Electroacupuncture
• Hemorrhagic shock
• Inflammation
• Neuromodulation
• Phrenic nerve stimulation
• Resuscitation
• Trigeminal nerve stimulation
• Vagus nerve stimulation

Postoperative ileus increases healthcare costs and reduces the postoperative quality of life (QOL). The aim of this study is to investigate effects and mechanisms of electroacupuncture (EA) at ST36 and PC6 on gastrointestinal motility in rat model of postoperative ileus.

Laparotomy was performed in 24 rats (control [n = 8], sham-EA [n = 8], and EA [n = 8]) for the implantation of electrodes in the stomach and mid-jejunum for recording of gastric and small intestinal slow waves. Electrodes were placed in the chest skin for electrocardiogram (ECG). Intestinal manipulation (IM) was performed in Sham-EA and EA rats after surgical procedures. Small intestinal transit (SIT), gastric emptying (GE), postoperative pain, and plasma TNF-α were evaluated in all rats.

(1) Compared with sham-EA, EA accelerated both SIT (P < 0.05) and GE (P < 0.05) and improved regularity of small intestinal slow waves. (2) Compared with the control rats (no IM), IM suppressed vagal activity and increased sympathovagal ratio assessed by the spectral analysis of heart rate variability from ECG, which were significantly prevented by EA. (3) EA significantly reduced pain score at 120 minutes (P < 0.05, vs 15 minutes) after the surgery, which was not seen with sham-EA. (4) Plasma TNF-α was increased by IM (P = 0.02) but suppressed by EA (P = 0.04) but not sham-EA.

The postoperative ileus induced by IM, EA at ST36 and PC6 exerts a prokinetic effect on SIT and GE, a regulatory effect on small intestinal slow waves and an analgesic effect on postoperative pain possibly mediated via the autonomic-cytokine mechanisms.

• Dysmotility
• Electroacupuncture
• Ileus
• Inflammation
• Pain

• Enteric nervous system
• IgA antibody response
• Intestinal homeostasis
• Parasympathetic nervous system
• Posterior vagotomy

• Animals
• CD4-Positive T-Lymphocytes/immunology
• Down-Regulation
• Immunity, Mucosal/immunology
• Immunoglobulin A/immunology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/innervation
• Intestine, Small/immunology
• Intestine, Small/innervation
• Male
• Mice
• Mice, Inbred BALB C
• Plasma Cells/immunology
• Vagotomy
• Vagus Nerve/physiology

Gastrointestinal functional recovery is an important factor affecting postoperative outcome. The aim of this study was to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on gastrointestinal function in women undergoing cesarean section.

150 pregnant women undergoing cesarean section were randomly allocated into TEAS, nonacupoint stimulation (sham group), and no stimulation (control group). The primary outcome was indications of gastrointestinal functional recovery and the secondary outcomes included time to first mobilization, postoperative hospital stay, daily living activities at one week after surgery, postoperative side-effects, and serum levels of gastroenterological hormones.

The time to first flatus in TEAS group was significantly shorter compared to control (P=0.004) and sham groups (P=0.003). The time to first oral liquid and solid intake was significantly shorter than that in control (P<0.001; P=0.021) and sham group (P=0.019; P=0.037). Besides, postoperative hospital stay was shorter in TEAS group than in control group (P=0.031) and sham group (P<0.001). TEAS also promoted daily living activities (P=0.001 versus control group and P=0.015 versus sham group). Postoperative complications were similar among all the groups except for the incidence of abdominal distention 24 h after surgery (P=0.013; P=0.040). The motilin level was increased by TEAS (P=0.014 versus control group and P=0.020 versus sham group).

TEAS accelerated gastrointestinal functional recovery after cesarean section, by reducing postoperative hospital length, and improved daily living activities after surgery. This effect was partially mediated by regulation of the gastroenterological hormones.

To investigate the effects of electroacupuncture (EA) at “Zusanli” (ST36) and “Shangjuxu”(ST37) on reducing inflammatory reaction and improving intestinal dysfunction in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi.

A total of 71 patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi were randomly assigned to control group (n=36) and treatment group (n=35). Patients in control group were given conventional therapies including fluid resuscitation, anti-infection, vasoactive agents, mechanical ventilation, supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in treatment group underwent 20 minutes of EA at ST36-ST37 twice a day for five days. At baseline, day 1, day 3, and day 7 after treatment, the plasma levels of procalcitonin (PCT), tumor necrosis factor-α (TNF-α), intestinal fatty acid-binding proteins (I-FABP), D-lactate, citrulline, and TCM quantitative score of intestinal dysfunction were measured and recorded, respectively. And days on mechanical ventilation (MV), length of stay in intensive care unit (ICU), and 28d mortality were recorded.

During treatment, the plasma levels of PCT, TNF-α, I-FABP, D-lactate, and TCM quantitative score of intestinal dysfunction were declining in both groups, while the treatment group showed a significant decline (P<0.05). Plasma levels of citrulline were increasing in both groups, while the treatment group showed a significant increase (P<0.05). However, there were no significant differences in the days on MV, length of stay in ICU, and 28d mortality between two groups (P>0.05).

EA at ST36-ST37 can reduce inflammatory reaction and has protective effects on intestinal function in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi.

This trial was registered at http://www.chictr.org.cn/(ChiCTR-IOR-17010910).

• electro-acupuncture
• inflammatory response
• intestinal dysfunction
• intraabdominal pressure
• sepsis
• syndrome of obstruction of the bowels qi

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Electroacupuncture/methods
• Female
• Humans
• Intensive Care Units
• Interleukin-1beta/blood
• Intestinal Obstruction/etiology
• Intestinal Obstruction/physiopathology
• Intestinal Obstruction/therapy
• Intestines/innervation
• Intestines/physiopathology
• Intra-Abdominal Hypertension/etiology
• Intra-Abdominal Hypertension/physiopathology
• Intra-Abdominal Hypertension/therapy
• Length of Stay
• Male
• Middle Aged
• Respiration, Artificial/statistics & numerical data
• Systemic Inflammatory Response Syndrome/blood
• Systemic Inflammatory Response Syndrome/complications
• Systemic Inflammatory Response Syndrome/physiopathology
• Treatment Outcome
• Tumor Necrosis Factor-alpha/blood
• Young Adult

The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti-inflammatory pathway has been described through VN's fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favoring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti-inflammatory properties, would be of interest to restore homeostasis in the microbiota-gut-brain axis.

• cholinergic anti-inflammatory pathway
• microbiota-gut-brain axis
• stress
• vagus nerve
• vagus nerve stimulation

• infectious diseases
• inflammation
• nerve stimulation
• neuromodulation

• Animals
• Electroacupuncture/methods
• Humans
• Immunomodulation/immunology
• Inflammation/immunology
• Neurons/immunology

• R01 GM084125 NIGMS NIH HHS
• R01 GM114180 NIGMS NIH HHS

• acetylcholine
• alpha7 nicotinic acetylcholine receptor
• inflammation
• sepsis
• vagus nerve

AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock.

METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation.

RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units (× 10⁵, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability.

CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure.

• Small bowel ischemia
• Hemorrhagic shock
• Peptides
• Microcirculation
• Proteolysis

• IK2 BX001277 BLRD VA
• R01 GM085072 NIGMS NIH HHS

• Acute-Phase Proteins
• Biomarkers/analysis
• Biomarkers/blood
• Chemokines
• Cytokines
• Humans
• Inflammation Mediators/analysis
• Intraabdominal Infections/diagnosis
• Intraabdominal Infections/pathology
• Intraabdominal Infections/therapy
• Sepsis/diagnosis
• Sepsis/pathology
• Sepsis/therapy

Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA) at Zusanli (ST36) could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a) EAN: EA nonchannel acupoints followed by scald injury; (b) EA: EA at ST36 after scald injury; (c) VGX/EA: vagotomy (VGX) before EA at ST36 and scald injury; (d) VGX/EAN: VGX before EAN and scald injury; (e) atropine/EA: applying atropine before scald injury and then EA at ST36; (f) atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO) and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

Objective. To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment. Research Design and Methods. The severe hemorrhagic shock model was reproduced in Sprague Dawley rats. Main Outcome Measures. Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection. Results. Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1. Conclusions. The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment.

In China, acupuncture has been considered an effective method for treating gastrointestinal (GI) dysfunction diseases for thousands of years. In fact, acupuncture has gained progressive acceptance from both practitioners and patients worldwide. However, the therapeutic effects and underlying mechanisms in treating GI dysfunction have not yet been established due to a lack of systematic and comprehensive review articles. Therefore, the aim of this review is to discuss the efficacy of acupuncture as a treatment for GI dysfunction and the associated underlying mechanisms. A search of PubMed was conducted for articles that were published over the past 10 years using the terms “acupuncture”, “gastrointestine”, and other relevant keywords. In the following review, we describe the effect and underlying mechanisms of acupuncture on GI function from the perspectives of GI motility, visceral sensitivity, the GI barrier, and the brain-gut axis. The dual regulatory effects of acupuncture may manifest by promoting gastric peristalsis in subjects with low initial gastric motility, and suppressing peristalsis in subjects with active initial motility. In addition, the regulation of acupuncture on gastric motility may be intensity-dependent. Our findings suggest that further studies are needed to investigate the effects and more systematic mechanisms in treating GI dysfunction, and to promote the application of acupuncture for the treatment of GI diseases.

• Acupuncture
• Gastrointestinal motility
• Gastrointestinal barrier
• Visceral sensitivity
• Brain-gut axis

• Abdominal Pain/physiopathology
• Abdominal Pain/therapy
• Acupuncture Therapy
• Animals
• Brain/physiopathology
• Enteric Nervous System/physiopathology
• Gastrointestinal Diseases/diagnosis
• Gastrointestinal Diseases/physiopathology
• Gastrointestinal Diseases/therapy
• Gastrointestinal Motility
• Gastrointestinal Tract/innervation
• Gastrointestinal Tract/physiopathology
• Humans
• Hyperalgesia/physiopathology
• Hyperalgesia/therapy
• Treatment Outcome

• Acute lung injury
• Electroacupuncture
• HMGB-1
• ST36

AIM: To investigate whether electroacupuncture ST36 activates enteric glial cells, and alleviates gut inflammation and barrier dysfunction following hemorrhagic shock.

METHODS: Sprague-Dawley rats were subjected to approximately 45% total blood loss and randomly divided into seven groups: (1) sham: cannulation, but no hemorrhage; (2) subjected to hemorrhagic shock (HS); (3) electroacupuncture (EA) ST36 after hemorrhage; (4) vagotomy (VGX)/EA: VGX before hemorrhage, then EA ST36; (5) VGX: VGX before hemorrhage; (6) α-bungarotoxin (BGT)/EA: intraperitoneal injection of α-BGT before hemorrhage, then EA ST36; and (7) α-BGT group: α-BGT injection before hemorrhage. Morphological changes in enteric glial cells (EGCs) were observed by immunofluorescence, and glial fibrillary acidic protein (GFAP; a protein marker of enteric glial activation) was evaluated using reverse transcriptase polymerase chain reaction and western blot analysis. Intestinal cytokine levels, gut permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran, and the expression and distribution of tight junction protein zona occludens (ZO)-1 were also determined.

RESULTS: EGCs were distorted following hemorrhage and showed morphological abnormalities. EA ST36 attenuated the morphological changes in EGCs at 6 h, as compared with the VGX, α-BGT and HS groups. EA ST36 increased GFAP expression to a greater degree than in the other groups. EA ST36 decreased intestinal permeability to FITC-dextran (760.5 ± 96.43 ng/mL vs 2466.7 ± 131.60 ng/mL, P < 0.05) and preserved ZO-1 protein expression and localization at 6 h after hemorrhage compared with the HS group. However, abdominal VGX and α-BGT treatment weakened or eliminated the effects of EA ST36. EA ST36 reduced tumor necrosis factor-α levels in intestinal homogenates after blood loss, while vagotomy or intraperitoneal injection of α-BGT before EA ST36 abolished its anti-inflammatory effects.

CONCLUSION: EA ST36 attenuates hemorrhage-induced intestinal inflammatory insult, and protects the intestinal barrier integrity, partly via activation of EGCs.

• Hemorrhagic shock
• Electroacupuncture
• ST36
• Cytokines
• Intestinal barrier
• Enteric glial cells

• Animals
• Bungarotoxins/administration & dosage
• Dextrans/metabolism
• Disease Models, Animal
• Electroacupuncture
• Enteric Nervous System/drug effects
• Enteric Nervous System/metabolism
• Enteric Nervous System/physiopathology
• Fluorescein-5-isothiocyanate/analogs & derivatives
• Fluorescein-5-isothiocyanate/metabolism
• Glial Fibrillary Acidic Protein/genetics
• Glial Fibrillary Acidic Protein/metabolism
• Intestine, Small/innervation
• Male
• Neuroglia/drug effects
• Neuroglia/metabolism
• Neuroglia/pathology
• Permeability
• Rats, Sprague-Dawley
• Shock, Hemorrhagic/genetics
• Shock, Hemorrhagic/metabolism
• Shock, Hemorrhagic/pathology
• Shock, Hemorrhagic/physiopathology
• Shock, Hemorrhagic/therapy
• Time Factors
• Tumor Necrosis Factor-alpha/metabolism
• Vagotomy
• Zonula Occludens-1 Protein/metabolism

• Abdominal adhesions
• Angiogenesis
• Electroacupuncture
• Inflammation
• ST36

• Abdominal Wound Closure Techniques
• Animals
• Cecum/pathology
• Electroacupuncture
• Inflammation/metabolism
• Inflammation/prevention & control
• Male
• Neovascularization, Pathologic/metabolism
• Neovascularization, Pathologic/prevention & control
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Random Allocation
• Rats, Sprague-Dawley
• Tissue Adhesions/pathology
• Tissue Adhesions/prevention & control
• Tumor Necrosis Factor-alpha/metabolism
• Vascular Endothelial Growth Factor A/metabolism