替米沙坦对糖尿病大鼠肾脏组织中内质网应激介导相关细胞凋亡的保护作用  

Protective effect of telmisartan on endoplasmic reticulum stress-related kidney cells apoptosis in diabeticrats

作　　者：陈玉凤[2] 张会娟[1] 沈育芬[1] 刘威[1] 贺捷[1] 李凤丽[1] 

机构地区：[1]郑州大学第一附属医院内分泌代谢科,450052 [2]新乡市中心医院内分泌代谢科

出　　处：《中华内分泌代谢杂志》2011年第10期849-852,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：探讨血管紧张素Ⅱ受体拮抗剂对糖尿病大鼠肾脏组织中内质网应激相关的细胞凋亡的影响。31只雄性SD大鼠分为正常对照组、糖尿病组、替米沙坦干预组。12周试验结束后测量大鼠体重、24h尿蛋白量，检测血糖、血胰岛素、血肌酐等。肾脏细胞凋亡用TUNEL法检测；肾脏细胞内质网应激信号通路分子糖调节蛋白78（GRP78）、caspase12和CHOP用免疫组化及实时定量PCR法检测。糖尿病组的血糖、24h尿蛋白量、血肌酐显著高于对照组（P〈0．05）；体重和血胰岛素较对照组低（P〈0．05）。替米沙坦干预组的24h尿蛋白量、血肌酐较糖尿病组明显减少（P〈0．05），凋亡指数也显著低于糖尿病组（P〈0．05）。大鼠内质网应激信号通路分子GRP78、caspase12、CHOP蛋白及其mRNA的表达，糖尿病组显著高于对照组和替米沙坦干预组（P〈0．05）。内质网应激参与了糖尿病大鼠肾脏细胞的凋亡，替米沙坦对内质网应激介导相关的肾脏细胞凋亡有保护作用。To investigate the effect of angiotensin receptor blocker （ARB） telmisartan on endoplasmic reticulum stress-related kidney ceils apoptosis in diabetic rats. 31 male SD rats were divided into 3 groups： normal control group, diabetic group, and telmisartan treated diabetic group. After 12 weeks＇ experiment, weight, 24 h urinary albumin excretion, blood glucose, serum insulin, and serum creatinine were determined. Renal cell apoptosis was examined by using TUNEL; Renal cell endoplasmic reticulum stress signaling pathway molecules glucose regulated protien 78 （ GRP78 ） , caspasel2, and CHOP were detected with immunohistochemistry and realtime PCR. 24 h urine protein and serum creatinine in diabetic group were significantly higher than those in the control group ; while body weight and plasma insulin were significantly lower than those in the control group （ P 〈 0. 05 ） ; Compared with diabetic group, 24 h urinary protein and serum creatinine were decreased significantly in telmisartan treated diabetic group（ P〈0. 05 ）. The apoptosis index of telmisartan treated group was significantly lower than that of diabetic group （P〈O. 05 ）. Endoplasmic reticulum stress signaling pathway molecules GRP78, caspasel2, CHOP protein and mRNA expression in diabetic group were significandy higher than those in control group （ P〈0. 05 ）, as well as in telmisartan treated group（ P〈0.05 ）. Endoplasmic reticulum stress took part in kidney cell apoptosis of the diabetic rat. Telmisartan possessed a protective effect on endoplasmic reticulum stress-related renal ceils apoptosis.

关 键 词：糖尿病肾病 内质网应激 细胞凋亡 替米沙坦 

分 类 号：R587.1[医药卫生—内分泌]