硫化氢与小鼠恶唑酮结肠炎肠黏膜损伤的相关性

背景：研究发现内源性气体递质H2S可能具有抗炎活性。关于H2S在溃疡性结肠炎（UC）中的作用，目前研究结果不一。目的：探讨H2S与恶唑酮诱导的小鼠实验性结肠炎肠黏膜损伤的相关性。方法：健康雄性昆明小鼠96只随机分为正常对照组、模型组、NH2OH组、NaHS组，后三组建立恶唑酮结肠炎模型，NH2OH组和NaHS组分别腹腔注射H2S合成关键酶胱硫醚B合酶（CBS）抑制剂NH2OH和H2S供体NaHS干预3d或7d。实验期间评估疾病活动指数（DAI）。干预结束后处死小鼠，取病变结肠组织行组织学损伤评分，以ELISA法测定白细胞介素-4（IL-4）含量，以realtimeRT—PCR测定CBSmRNA表达，同时检测血浆H2S含量。结果：模型组、NH2OH组、NaHS组DAI评分、结肠黏膜组织学损伤评分和结肠组织IL-4含量、CBSmRNA表达明显高于正常对照组，NH2OH组高于模型组，NaHS组低于模型组，差异均有统计学意义（P〈0．05）。NH2OH组血浆H2S含量明显低于正常对照组和模型组，NaHS组明显高于正常对照组和模型组，差异均有统计学意义（P〈0．05）。结论：内源性H2S与小鼠恶唑酮结肠炎的肠黏膜损伤之间存在明显相关性，可能起抗炎和肠黏膜保护作用。

Association of Hydrogen Sulfide with Intestinal Mucosal Injury in Mice with Oxazolone-induced Colitis

Background： Hydrogen sulfide （H2 S ） is an endogenous gaseous mediator that may exhibit anti-inflammatory activities, however, whether H2 S is involved in the pathogenesis of ulcerative colitis （UC） is a controversy. Aims ： To investigate the association of H2 S with intestinal mucosal injury in mice with oxazolone-induced experimental colitis. Methods： Ninety-six healthy male Kunming mice were randomized into four groups： normal control group, model group, NH2OH group and NariS group. Experimental colitis was induced by oxazolone in model group, NH2OH group and NariS group. For mice in NH2 OH group, NH2 OH, an inhibitor of the key enzyme in H2 S synthesis - cystathionine beta-synthase （ CBS）, was injected intraperitoneally for 3 or 7 days ; while for mice in NariS group, NariS, a donor of H2S, was injected intraperitoneally. Disease activity index （DAI） was assessed during the experiment. All mice were sacrificed on day 3 or day 7, their diseased colon was resected for histological examination, and interleukin-4 （IL-4） level was detected by ELISA method, CBS mRNA expression was determined by real time RT-PCR. Plasma H2S level was measured simultaneously. Results： DAI, histological damage score, and levels of IL-4 and CBS mRNA in colonic tissues were significantly higher in model group, NH2 OH group and NariS group than in normal control group （ P 〈 0.05 ）. All these parameters were higher in NH2 OH group than in model group （P 〈 0.05 ）, and were lower in NariS group than in model group （ P 〈 0.05 ）. Plasma H2 S level in NH2 OH group was significantly lower than that in normal control group and model group （ P 〈 0.05 ）, while that in NariS group was significantly higher than that in normal control group and model group （ P 〈 0.05 ）. Conclusions： Endogenous H2 S was closely correlated with intestinal mucosal injury in mice with oxazolone- induced experimental colitis, and might play an anti-inflammatory and intestinal mucosal protective effect.