Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jan 7, 2008; 14(1): 29-37
Published online Jan 7, 2008. doi: 10.3748/wjg.14.29
Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion
Wei-Xing Chen, Fang Wang, Yu-Ying Liu, Qing-Jiang Zeng, Kai Sun, Xin Xue, Xiang Li, Ji-Ying Yang, Li-Hua An, Bai-He Hu, Jin-Hui Yang, Chuan-She Wang, Zhi-Xin Li, Lian-Yi Liu, Yan Li, Jun Zheng, Fu-Long Liao, Dong Han, Jing-Yu Fan, Jing-Yan Han
Wei-Xing Chen, Fang Wang, Yu-Ying Liu, Qing-Jiang Zeng, Kai Sun, Xin Xue, Xiang Li, Ji-Ying Yang, Li-Hua An, Bai-He Hu, Jin-Hui Yang, Chuan-She Wang, Zhi-Xin Li, Lian-Yi Liu, Yan Li, Jun Zheng, Fu-Long Liao, Dong Han, Jing-Yu Fan, Jing-Yan Han, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing 100083, China
Wei-Xing Chen, Ji-Ying Yang, Jun Zheng, Department of Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
Chuan-She Wang, Zhi-Xin Li, Jing-Yan Han, Department of Integrated Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100083, China
Correspondence to: Jing-Yan Han, MD, PhD, Chairman of Department of Integrated Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100083, China. kan@chuigaku.co.jp
Telephone: +86-10-82802862
Fax: +86-10-82802996
Received: April 17, 2007
Revised: September 28, 2007
Published online: January 7, 2008
Abstract

AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice.

METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-min reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence.

RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1.

CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.

Keywords: Ischemia/reperfusion; Notoginsenoside R1; Leukocytes adhesion; E-selectin; Hepatic injury