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目的观察舒芬太尼与APETx2预先给药对浸水束缚应激(WIRS)大鼠胃组织酸敏感离子通道3(ASIC3)表达及胃黏膜损伤的影响。方法 40只雄性Wistar大鼠随机等分为对照组(C组)、应激组(W组)、舒芬太尼预先给药组(S组,腹腔内注射舒芬太尼25μg/kg)及ASIC3特异性拮抗剂APETx2预先给药组(A组,腹腔内注射APETx2 25μg/kg)。采用WIRS法复制应激性胃黏膜损伤模型,于应激6 h后留取标本测定溃疡指数(UI);黄嘌呤氧化酶法测定胃组织超氧化物歧化酶(SOD)活力与硫代巴比妥酸法测定丙二醛(MDA)含量;免疫组化和免疫印迹法测定胃组织ASIC3蛋白表达。结果与C组比较,W组、S组及A组的UI值显著升高(P均<0.01),SOD值显著下降(P均<0.01),MDA值显著升高(P均<0.01),胃组织ASIC3蛋白表达显著上调(P均<0.01)。与W组比较,S组及A组的UI值显著下降(P均<0.01),SOD值显著升高(P均<0.01),MDA值显著下降(P均<0.01);A组的ASIC3蛋白表达显著下调(P<0.01),S组差异无统计学意义(P>0.05)。结论 APETx2调控胃组织ASIC3蛋白表达,逆转氧自由基代谢失衡起胃黏膜保护作用;舒芬太尼同样通过逆转氧自由基代谢失衡起胃黏膜保护作用,但其作用机制并非通过调控ASIC3完成。
Objective To observe the effects of sufentanil and APETx2 pretreatment on the expression of gastric acid sensitive ion channel 3 (ASIC3) and gastric mucosal injury in water immersion restraint stress (WIRS) rats. Methods Forty male Wistar rats were randomly divided into control group (C group), stress group (W group), sufentanil preconditioning group (S group, intraperitoneal injection of sufentanil 25μg / kg) and ASIC3-specific antagonist APETx2 premedication group (Group A, APETx2 25μg / kg). WIRS method was used to replicate the stress gastric mucosa injury model, and the ulcer index (UI) was taken after 6 h of stress. The activity of superoxide dismutase (SOD) in gastric tissue was measured with xanthine oxidase method. The contents of malondialdehyde (MDA) were determined by tau acid method. The expression of ASIC3 protein in gastric tissues was detected by immunohistochemistry and Western blot. Results Compared with group C, the UI values of W group, S group and A group were significantly increased (P <0.01), SOD value decreased significantly (P <0.01), MDA value increased significantly (P <0.01) The expression of ASIC3 in gastric tissue was significantly up-regulated (all P <0.01). Compared with W group, the UI value of S group and A group decreased significantly (P <0.01), SOD value increased significantly (P <0.01), MDA value decreased significantly (P <0.01) (P <0.01). There was no significant difference in S group (P> 0.05). Conclusions APETx2 regulates the expression of ASIC3 in gastric tissue and reverses the protective effect of gastric mucosal injury by unbalanced oxygen free radical metabolism. Sufentanil also protects gastric mucosa by reversing the metabolic imbalance of oxygen free radicals, but its mechanism of action is not mediated by the regulation of ASIC3.