葡萄籽原花青素对顺铂所致小鼠肾毒性作用的影响  

Effect of grape seed proanthocyanidin on cisplatin-induced nephrotoxicity in mice

作　　者：高兆丽[1] 刘广义[1] 李星[1] 胡昭[1] 杨向东[1] 江蓓[1] 李宪花[1] 

机构地区：[1]山东大学齐鲁医院泌尿内科,山东济南250012

出　　处：《中国病理生理杂志》2014年第2期313-317,共5页Chinese Journal of Pathophysiology

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。AIM ： To study the protective effect of grape seed proanthocyanidin （GSP） on nephrotoxicity in- duced 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 adminis- tration of GSP at dose of 500 mg/kg, n = 15 ） and CP ＋ GSP group （ intragastric administration of GSP 30 min prior to intra- peritoneal injection of C P 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 ni- trogen 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 tis- sues 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.

关 键 词：顺铂 葡萄籽原花青素 肾毒性 内质网应激 

分 类 号：R595.4[医药卫生—内科学] R692.5[医药卫生—临床医学]