【摘要】 目的:探讨葡萄籽原花青素(GSP)对顺铂(CP)肾毒性作用的防护及可能机制。方法:雄性C57小鼠分为4组:正常对照组(N组,n=10)、CP组(腹腔注射20 mg/kg CP,n=20)、GSP组(第1天及第3天灌胃GSP500 mg/kg,n=15)和CP+GSP组(腹腔注射CP 30 min前给予500 mg/kg GSP灌胃,第3天灌胃等量的GSP,n=20)。给药后第5天取血,肾组织病理HE染色,应用蛋白印迹法和免疫组化法检测小鼠葡萄糖调节蛋白78(GRP78)和磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达。结果:与N组比较,CP组肾脏指数升高,血尿素氮和血清肌酐水平升高(P<0.05),肾病理损伤明显,肾组织GRP78和p-ERK蛋白表达增加(P<0.05)。与CP组相比,CP+GSP组肾脏指数降低,血尿素氮和血清肌酐水平下降(P<0.05),肾病理损伤减轻,GRP78和p-ERK蛋白表达明显降低(P<0.05)。结论:GSP能明显降低CP所致的肾毒性,其机制与GSP下调CP导致的内质网应激有关。更多还原

【Abstract】 AIM:To study the protective effect of grape seed proanthocyanidin(GSP) on nephrotoxicity induced by cisplatin(CP) in mice.METHODS:Male C57 mice were randomly divided into 4 groups:control group(N group,n = 10),CP group(intraperitoneal injection of CP at dose of 20 mg / kg,n = 20),GSP group(intragastric administration of GSP at dose of 500 mg / kg,n = 15) and CP + GSP group(intragastric administration of GSP 30 min prior to intraperitoneal injection of CP and intragastric administration of the same dose of GSP 72 h later,n = 20).On the 5th day after CP treatment,blood and kidney samples were collected.The renal pathological changes were examined by HE staining.The protein expression of glucose-regulated protein 78(GRP78) and phosphorylated extracellular signal-regulated kinase(p-ERK) was examined by Western blotting and immunohistochemical staining.RESULTS:Renal index,blood urea nitrogen and serum creatinine were significantly higher in CP group than those in N group.The renal tissues were heavily damaged in CP group.The protein expression of GRP78 and p-ERK increased in CP group compared with N group.GSP treatment alleviated the increase in the renal index,blood urea nitrogen and serum creatinine.The damages of the renal tissues were attenuated.The protein expression of GRP78 and p-ERK was obviously reduced in CP + GSP group compared with CP group.CONCLUSION:GSP prevents kidney from CP-induced damage by suppression of endoplasmic reticulum stress.更多还原