外源性H_2S通过激活K_(ATP)通道减轻大鼠胃缺血再灌注引起的胃黏膜损伤

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本文旨在观察外源性硫化氢(hydrogen sulfide,H2S)供体NaHS预处理对大鼠胃缺血再灌注(gastric ischemia-reperfusion,GI-R)损伤的影响及其可能的作用机制。实验分5组:假手术(sham)组、GI-R组、NaHS组、格列苯脲(glibenclamide)组和吡那地尔(pinacidil)组。采用夹闭雄性Sprague-Dawley(SD)大鼠腹腔动脉30min再灌注1h,建立GI-R损伤模型。采用Adobe Photoshop软件分析计算GI-R引起的胃黏膜损伤面积,利用HE染色分析GI-R引起的胃黏膜损伤深度,通过比色法测定血浆中H2S的含量。结果显示,与假手术(sham)组相比,GI-R组胃黏膜损伤面积和损伤深度明显增加;NaHS预处理能够显著减小GI-R引起的胃黏膜损伤面积和损伤深度;但是NaHS预处理14d对血浆中的H2S浓度没有显著的影响。与NaHS预处理组相比,GI-R前给予ATP敏感K+通道(KATP)阻断剂格列苯脲和NaHS预处理,加重GI-R引起的胃黏膜损伤程度;与GI-R组相比,单独给予KATP通道开放剂吡那地尔能够抑制GI-R的损伤作用,保护胃黏膜。上述结果提示,外源性H2S通过开放KATP通道减轻GI-R引起的胃黏膜损伤,起到保护胃黏膜的作用。 This article aims to observe the effect of exogenous hydrogen sulfide (H2S) donor NaHS preconditioning on gastric ischemia-reperfusion (GI-R) injury in rats and its possible mechanism. The experiment was divided into 5 groups: sham group, GI-R group, NaHS group, glibenclamide group and pinacidil group. The GI-R injury model was established by clipping the celiac artery of male Sprague-Dawley (SD) rats for 30 min and reperfusion for 1 h. The gastric mucosal lesion area caused by GI-R was analyzed by Adobe Photoshop software. The gastric mucosal lesion depth induced by GI-R was analyzed by HE staining. The content of H2S in plasma was determined by colorimetry. The results showed that gastric mucosal lesion area and lesion depth were significantly increased in GI-R group compared with sham group. NaHS pretreatment significantly reduced gastric mucosal lesion area and lesion depth induced by GI-R; however, NaHS preconditioning Treatment 14d had no significant effect on the concentration of H2S in plasma. Compared with NaHS pretreatment group, GI-R pretreatment with glibenclamide and NaHS, an ATP-sensitive K + channel (KATP) antagonist, increased GI-R-induced gastric mucosal injury; compared with GI-R group Pinagnaide, a KATP channel opener alone, could inhibit GI-R injury and protect gastric mucosa. The above results suggest that exogenous H2S can relieve gastric mucosal injury caused by GI-R through the opening of KATP channels and play a role in the protection of gastric mucosa.
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