Akt参与室旁核内注射微量催产素减轻大鼠胃缺血-再灌注损伤

Protective effect of Akt on gastric ischemia-reperfusion injury by microinjection of oxytocin into the paraventricular nucleus in rats

目的研究室旁核(PVN)内注射微量催产素(OT)对大鼠胃缺血再灌注(GI-R)损伤的影响及其局部的分子机制。方法用夹闭大鼠腹腔动脉30 min,再灌注1 h的GI-R损伤模型,于单侧PVN内注射微量OT。计数胃黏膜损伤指数后,用免疫组化及免疫印迹观察胃黏膜细胞p-Akt和caspase-3蛋白表达。结果PVN内注射微量OT(24、120、600和3000 ng)呈剂量依赖性减轻GI-R损伤,并明显增加胃黏膜细胞的Akt表达和减少caspase-3的表达。侧脑室给予OT特异性拮抗剂阿托西班(atosiban)后消除OT对大鼠GI-R损伤的影响。结论PVN微量注射OT后通过增加胃黏膜细胞Akt表达,抑制caspase-3的表达,减轻GI-R损伤。

Objective To observe the effect of microinjection of oxytocin （OT） into paraventricular nucleus （PVN） on gastric ischemia-reperfusion （GI-R） injury and its molecu-lar mechanism. Methods GI-R injury was induced in rats by clamping the celiac artery for 30 rain and followed by reperfusing for 1 h. A cannula was inserted into the unilateral PVN for microinjection of OT. The gastric mucosal injury index was counted grossly. The expressions of Akt and caspase-3 in rat gastric mucosa were examined by Western blot and by immunohistochemistry. Results Mi- croinjection of OT into PVN dose-dependently allevated gastric mucosal injury subjected to GI-R. Microinjection OT into PVN significantly increased the expression of Akt protein and decreased the level of caspase-3 in gastric mucosal following GI-R. The effects of OT were prevented by pretreatment with OT receptor antagonist atosiban into the lateral cerebral ventricle. Conclusion Microinjection of OT into PVN significantly protected against GI-R injury. These effects of OT are mediated by its receptors. The mechanisms are mediated by increasing Akt expression, which in turn inhibits caspase-3 expression.