修回日期: 2026-03-20
接受日期: 2026-03-23
在线出版日期: 2026-03-28
炎症性肠病(inflammatory bowel disease, IBD)是一类以慢性肠道炎症为主要特征的消化系统疾病, 包括溃疡性结肠炎和克罗恩病, 对患者身心健康和生活质量造成严重影响. 尽管目前免疫抑制剂、生物制剂等多种治疗手段可以在一定程度上缓解IBD症状, 但总体疗效有限, 复发率高且存在较明显的不良反应. 高压氧治疗(hyperbaric oxygen therapy, HBOT)作为一种通过提高组织氧合改善炎症微环境的新兴疗法, 近年来在IBD治疗领域受到广泛关注. 本文结合HBOT在IBD中的作用机制以及最新临床研究和系统评价数据评估其临床疗效和安全性, 进一步探讨其作为IBD辅助治疗手段的局限性及应用前景, 旨在为未来临床实践和科学研究提供参考.
核心提要: 高压氧治疗作为炎症性肠病(inflammatory bowel disease, IBD)治疗的新兴疗法近年来受到广泛关注. 本文根据高压氧在IBD治疗中的作用机制、结合最新临床研究结果和系统评价数据评估其临床疗效和安全性, 并探讨高压氧作为辅助治疗在IBD治疗中的不足之处及应用前景, 旨在为未来临床实践和科学研究提供参考.
引文著录: 李哲恒, 葛文松. 高压氧在炎症性肠病治疗中的研究进展. 世界华人消化杂志 2026; 34(3): 236-241
Revised: March 20, 2026
Accepted: March 23, 2026
Published online: March 28, 2026
Inflammatory bowel disease (IBD) is a digestive disorder characterized mainly by chronic intestinal inflammation, including ulcerative colitis and Crohn's disease, posing a significant impact on patients' physical and mental health and quality of life. Although various traditional treatment methods such as immunosuppressants and biological agents can alleviate IBD symptoms to a certain extent, their overall efficacy remains limited, with high recurrence rate and significant adverse effects. Hyperbaric oxygen therapy (HBOT), as an emerging therapy that improves the inflammatory microenvironment by enhancing tissue oxygenation, has received extensive attention in IBD treatment in recent years. This article discusses the clinical efficacy and safety of HBOT in IBD based on its mechanism of action, drawing on the latest clinical trial data and systematic reviews. Furthermore, it evaluates the shortcomings and application prospects of HBOT as an adjunct treatment for IBD, aiming to provide a reference basis for clinical practice and future research.
- Citation: Li ZH, Ge WS. Hyperbaric oxygen therapy in inflammatory bowel disease: Current evidence and research progress. Shijie Huaren Xiaohua Zazhi 2026; 34(3): 236-241
- URL: https://www.wjgnet.com/1009-3079/full/v34/i3/236.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v34.i3.236
炎症性肠病(inflammatory bowel disease, IBD)是一组慢性、易复发的消化道炎症性疾病, 主要包括克罗恩病(Crohn's disease, CD)和溃疡性结肠炎(ulcerative colitis, UC), 其发病机制复杂, 通常涉及免疫系统异常、遗传易感性、环境因素以及肠道微生态失衡等多重因素[1,2]. 该病往往始于青少年时期, 并且全球发病率持续上升, 尤其在新兴工业化国家和地区, 给全球公共卫生带来了重大挑战[3-5]. IBD患者常表现为腹泻、腹痛、消化道出血以及体重减轻等症状, 严重影响患者的身体健康和生活质量[6,7]. 同时, IBD患者还面临较高的心理压力以及焦虑、抑郁风险, 疾病的慢性迁延和反复发作进一步加重了其心理负担[8,9]. 目前, IBD的治疗主要依赖于药物, 包括糖皮质激素、免疫调节剂、生物制剂和小分子药物等, 主要用于控制肠道炎症、诱导缓解和维持缓解[10,11]. 然而, 现有药物的疗效有限且存在一定不良反应, 部分患者出现药物应答不佳或相关并发症, 从而不得不接受外科手术干预[12,13], 亟需新的辅助治疗手段[14,15]. 高压氧治疗(hyperbaric oxygen therapy, HBOT)作为一种非常规治疗方法, 主要通过在高于大气压的环境下吸入纯氧, 提高血液和组织氧分压, 改善组织缺氧状态, 调节炎症反应并促进组织修复[16,17]. HBOT已被广泛应用于缺血性疾病、慢性创面、放射性损伤及部分神经系统疾病的治疗, 并展现出良好的疗效和安全性[18,19]. 近年来, 随着HBOT在IBD领域的临床和基础研究逐渐增多, 越来越多的研究证据[20-22]提示HBOT可以通过抗炎、抗氧化、促进血管新生和免疫调节等机制促进肠黏膜修复, 缓解疾病活动度. 基于此, 本文综述了HBOT在IBD治疗中的最新研究进展, 评估其临床应用价值, 并探讨未来的研究方向和临床应用策略.
HBOT是一种在高压环境下吸入100%纯氧的治疗方法, 可显著提高血液和组织中的氧分压. 其核心原理在于利用高压环境大幅增加氧气的溶解度, 使氧分子更有效地渗透入血浆和缺氧的组织中, 从而改善局部的氧供状态. 与常压吸氧相比, HBOT可提高肠道组织含氧量, 从而促进细胞代谢和缺血组织修复, 进而有利于受损肠黏膜的修复愈合[23]. 此外, 还有研究[24]显示HBOT通过提高氧分压促进细胞线粒体功能恢复, 显著提高了线粒体氧化磷酸化能力.
HBOT对炎症调节的影响主要体现在抑制促炎因子的表达和降低氧化应激水平两个方面. 首先, HBOT能够通过干扰核因子-κB(nuclear factor kappaB, NF-κB)信号通路及其抑制因子的活性, 阻断促炎信号的传导, 降低肿瘤坏死因子-α(tumor necrosis factor alpha, TNF-α)、IL-6等炎症介质的释放, 从而缓解炎症状态. 例如, 在多种炎症模型中, HBOT治疗后促炎细胞因子浓度显著下降, 并伴随症状的改善[25,26]. 在IBD模型中, HBOT通过调节促炎因子水平减轻肠道炎症, 促进黏膜修复; 同时HBOT降低了NF-κB的表达, 抑制其下游炎症反应, 进一步证实了其抗炎作用[27,28]. 在糖尿病慢性创面和IBD等慢性炎症状态下, HBOT通过减少活性氧的产生和氧化损伤, 改善细胞功能, 促进炎症消退和组织愈合[27,29]. 此外, HBOT通过减少氧化应激反应, 增强抗氧化酶活性, 减轻氧自由基介导的组织损伤, 在短期内诱导适度氧化应激, 激活内源性抗氧化系统, 如超氧化物歧化酶、过氧化氢酶等的活性, 建立抵御氧化损伤的防御机制[30]. 相关研究显示[29,31], HBOT治疗能够降低血浆中的丙二醛和蛋白质羰基水平的同时提高抗氧化酶活性从而促进组织修复.
HBOT作为一种IBD辅助治疗手段的临床价值近年来逐渐受到关注. 多项临床研究显示, HBOT能够显著提高患者的临床缓解率并改善临床症状, 尤其是在难治性IBD患者中表现出积极的治疗效果.
在针对中重度UC患者采用HBOT联合类固醇药物治疗的两项Ⅱ期临床试验中, ⅡA期的接受HBOT的患者在研究第5 d和第10 d达到临床缓解的比例更高(50% vs 0%, P = 0.04), 且住院期间需要行结肠切除术的可能性更低(0% vs 38%, P = 0.07)[35]. 而另一项评估HBOT给药策略的ⅡB期试验发现, 5 d HBOT可带来更显著的疾病活动度下降(P = 0.03), 并进一步证实了ⅡA期试验中观察到的总体疗效, 提示HBOT具有较好的辅助治疗潜力[36]. 此外, 相应的模型研究预测, 在急性UC发作时激素早期联合HBOT与常规治疗相比, 不仅降低再住院率、急诊手术率和死亡率, 还显示出良好的经济效益比[37]. 这表明HBOT在临床上能够提升激素治疗效果的同时, 也降低了疾病的并发症发生, 改善患者的长期预后. 系统评价进一步证实了HBOT联合常规治疗可提高IBD患者的临床应答率. 一项纳入2151例患者的Meta分析显示, UC患者采用常规治疗联合HBOT治疗组临床应答率高达83%, 且复发率显著降低, 提示HBOT的辅助作用不仅体现在症状缓解上, 还可能延长疾病缓解期[38]. 然而, 现有部分研究结果仍存在差异, 并且关于HBOT治疗的最佳方案、疗程及适应症范围尚需进一步探讨与验证[39].
肛周瘘管性CD作为CD的一种严重表现, 显著影响患者的生活质量, 且治疗难度较大. 近年来, 随着HBOT在IBD领域的应用研究逐渐增多, 其在促进瘘管愈合方面展现出了良好潜力. 初期在单个病例的尝试应用取得了良好效果[40,41], 随后的小样本研究亦得到类似结果. 一项纳入10例患者的系列病例研究显示[42], 在标准内科治疗基础上联合HBOT后, 80%的患者瘘管完全愈合. 近年来一项纳入了16项研究[43]共164名患者的系统评价和Meta分析显示, HBOT在难治性肛瘘患者中瘘管整体的综合临床应答率为87%, 临床缓解率为59%. 而瘘管亚组分析如肛周瘘、肠皮瘘和直肠阴道瘘的总体临床应答分别为89%、84%和29%. 另一项研究[44]评估了HBOT对瘘管愈合的长期影响, 共纳入20例病程小于6 mo的瘘管患者, 所有患者均接受40次HBOT治疗后评估疗效, 结果显示患者的肛周疾病活动指数(perianal disease activity index, PDAI)从7.5降至4(P<0.001), 其中65%的患者PDAI<4, 肛周磁共振成像改良的van Assche指数的中位数评分从9.2降至7.3(P = 0.004), 并且12人获得临床应答, 4人获得临床缓解. 此外, 有研究发现[27], HBOT可改善肠道微生物群的失调, 并减轻肠道及全身炎症; HBOT不仅降低了C反应蛋白和CD活动指数, 还提高了肠道微生物的多样性, 改变了微生物组成, 尤其是Escherichia的相对丰度显著下降, 而Bifidobacterium和Clostridium XIVa的丰度有所增加; HBOT与生物制剂ustekinumab联合使用时, 患者的临床反应和缓解率也有所提高[27]. 尽管目前随机对照试验数据尚不充分, 但多项观察性研究和病例报道均支持HBOT作为难治性瘘管性CD的有效辅助治疗方法[43,45].
坏疽性脓皮病(pyoderma gangrenosum, PG)是一种罕见且难治的中性粒细胞性溃疡性皮肤病, 多表现为疼痛性皮肤溃疡, 常与IBD等自身免疫性疾病相关. PG的发病机制尚未完全明确, 目前认为可能与免疫系统异常调节有关, 尤其涉及Th17/Th1免疫失调、IL-1β/IL-36信号通路及肠-皮肤免疫轴的相互作用, 进而导致中性粒细胞过度浸润和炎症反应[46]. 在IBD患者中, PG发病率较高, 且常与疾病活动度相关, 提示其作为IBD的肠外表现之一, 临床诊断依赖于排除感染及其他溃疡性皮肤病变[47,48].
PG的传统系统治疗目前仍以糖皮质激素及其他免疫抑制剂为主, 难治病例可进一步采用抗TNF-α等生物制剂, 但现有治疗总体疗效存在个体差异, 且仍伴有复发及严重感染等不良反应风险[49,50]. 近年来, HBOT作为一种辅助治疗手段, 在PG的治疗中显示出一定临床应用价值. HBOT通过提供高浓度氧气, 改善局部组织缺氧和微循环, 促进血管生成与伤口愈合, 并具备免疫调节和抗炎作用, 从而加快溃疡修复[51,52].
HBOT联合免疫抑制治疗有助于促进PG皮肤溃疡的愈合, 缩短病程, 减少复发. 例如, 一项纳入6例合并PG的CD患者的观察性研究显示[53], HBOT治疗所有PG患者愈合率达到100%, 显示出良好的疗效. 此外, HBOT与阿达木单抗等生物制剂联合应用, 可实现临床完全缓解[54]. 病例报道亦证实, HBOT辅助治疗能够控制PG炎症进展, 从而改善预后[55,56].
慢性抗生素难治性贮袋炎(chronic antibiotic-refractory pouchitis, CARP)是UC患者在进行回肠贮袋肛管吻合术后出现的一种严重且难以治疗的并发症, 主要特征表现为贮袋持续性炎症, 通常表现为腹痛、腹泻、排便急迫等症状, 且对常规抗生素治疗无效, 严重影响患者生活质量和预后. HBOT能够显著改善CARP患者的临床症状及内镜表现, 一项研究表明[57]接受HBOT治疗后, 患者改良贮袋炎疾病活动指数症状评分从治疗前的3.19下降至1.91, 内镜评分在贮袋的不同部位均有显著下降(例如贮袋体部内镜评分从2.34降至1.29), 提示贮袋炎症明显缓解.
CD并发直肠阴道瘘是女性CD患者较少见但极具致残性的并发症, 常表现为阴道排气、排便或脓性分泌物, 明显影响生活质量. HOT-REVA前瞻性试点研究纳入了9例既往内科及外科治疗失败的患者, 完成30次HBOT后, 3 mo随访时无一例达到瘘管闭合, PDAI评分及生活质量指标亦未见明显改善, 提示HBOT单独用于此类难治性直肠阴道瘘的疗效有限[58]. 前文所述Meta分析也显示直肠阴道瘘亚型的总体临床应答率仅为29%, 显著低于其他亚型, 因此其在HBOT适应证中的具体定位仍有待进一步研究明确.
HBOT在IBD中的应用日益广泛, 系统评价和Meta分析结果显示其耐受性良好且副作用较轻微. 例如, 一项纳入19项研究[59]共809名IBD患者的系统综述指出, 约15%的患者经历了轻微不良事件, 且这些副作用均为可逆性, 未见严重安全问题. 同样, 在针对CARP的回顾性病例系列研究中, HBOT总体耐受性良好, 轻微的耳压伤和高压氧引起的短暂性近视变化各占10.9%, 均为短暂性且未导致治疗中断[57]. 针对CD瘘管患者的系统评价显示, HBOT的副作用发生率极低, 约为51.7/10000例不良事件, 且未见严重不良事件报告[43]. 此外, 一项涉及小肠狭窄型CD患者的前瞻性研究中[60], 绝大多数患者对HBOT耐受良好, 仅有一例出现鼓膜出血, 未见其他严重不良反应. 上述结果提示, HBOT作为一种IBD辅助治疗手段具有较好的安全性.
HBOT作为一种新兴的IBD辅助治疗方法, 显示出良好的治疗潜力, 尤其是在控制炎症、减轻氧化应激、促进受损组织修复等方面发挥出独特作用. 然而, HBOT在IBD临床应用过程中仍面临诸多挑战, 并存在进一步优化的空间. 首先, 标准化治疗流程的建立是当前亟待解决的核心问题. 尽管已有多项临床研究和系统评价证实HBOT对UC及CD相关瘘管的积极疗效, 但不同研究中HBOT的具体方案存在较大差异, 包括治疗压力、时长、频次及总疗程尚无统一标准. 其次, 患者依从性问题也需解决. HBOT治疗通常需要患者多次进入高压氧舱, 单次治疗耗时较长, 这对患者的时间安排均提出挑战. 当前相关经济学分析较少, 缺乏对HBOT成本效益的系统评价, 限制了其在更大范围内的推广应用. 最后, 提高医生对HBOT在IBD治疗中价值认识同样重要. 尽管HBOT的基础研究和临床试验结果不断积累, 但其作为辅助治疗手段的临床指南尚未完善, 部分医生对其机制、适应症及疗效缺乏足够了解, 限制了其在日常临床中的广泛使用. 建立国际多中心的HBOT临床数据注册系统, 可系统收集治疗效果和安全性数据, 为制定规范的临床指南提供依据. 同时, 通过专业培训和学术推广, 增强医务人员对HBOT的认知, 有助于将其纳入IBD综合治疗体系中.
综上所述, HBOT在IBD中的临床应用前景广阔, 但尚需在标准化治疗流程、经济性评价、患者依从性及临床推广等方面继续探讨. 未来应多开展多中心、高质量的随机对照临床试验, 完善治疗方案, 评估成本效益, 为患者带来更有效、安全的治疗选择.
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学科分类: 胃肠病学和肝病学
手稿来源地: 上海市
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科学编辑: 刘继红 制作编辑:张砚梁