EP2受体激动剂对脓毒症小鼠相关急性肾损伤的保护机制研究

Protective effect of prostaglandin E receptor 2 agonist on septic acute kidney injury in mice and its mechanism

目的:研究E型前列腺素受体2(prostaglandin E receptor 2,EP2)激动剂Butaprost对脓毒症急性肾损伤小鼠的保护作用及其可能机制。方法:40只小鼠随机分为正常组、假手术组、盲肠结扎穿刺(cecum ligation and puncture,CLP)组、CLP+Butaprost组,每组10只。CLP法建立脓毒症小鼠急性肾损伤模型。小鼠死亡时取小鼠肾脏标本并采集小鼠的静脉血。采用全自动血液分析仪检测小鼠血清肌酐(serum creatinine,SCr)及尿素氮(blood urea nitrogen,BUN);HE染色观察肾脏组织病理变化;Western Blot检测肾脏组织CCAAT/增强子结合蛋白同源蛋白(CCAT/enhancer-blinding protein homologous protein,CHOP)、葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)蛋白表达。结果:与CLP组比较,CPL+Butaprost组小鼠肾脏病理有改善,SCr、BUN降低及CHOP、GRP78蛋白表达减少(P<0.05)。结论:Butaprost通过激活EP2调控内质网应激进而延缓肾脏损伤以发挥保护作用。

Objective:To study the protective effect on mechanism of prostaglandin E receptor 2(EP2)agonist Butaprost on septic acute kidney injury in mice.Methods:Forty mice were randomly divided into Normal group,sham operation group,cecum ligation and puncture(CLP)group,CLP treated with Butaprost group,10 mice in each group.Acute renal injury model of sepsis was induced by CLP.Kidney samples and venous blood were collected at the time of death of mice.Serum creatinine(SCr)and blood urea nitrogen(BUN)were detected by automatic blood analyzer.The pathological changes of kidney tissue were observed by HE staining and the protein expressions of CCAT/enhancer-blinding protein homologous protein(CHOP)and glucose-regulated protein 78(GRP78)in kidney tissue were detected by Western Blot.Results:Compared with CLP group,pathology of CLP+Butaprost group was improved,SCr and BUN were decreased,and protein expressions of CHOP and GRP78 were decreased(P<0.05).Conclusion:Butaprost regulate endoplasmic reticulum stress and delay the progression of renal damage by activating EP2 to exert kidney protective effects.