ACE2对糖尿病大鼠肾小球足细胞的影响及厄贝沙坦干预作用的研究  

Study of influence of ACE2 on glomerular podocytes in diabetic rats and the effects of irbesartan

作　　者：陈欢[1] 沈洁[1] 李章芳[1] 唐杰龙[1] 朱艳[1] 胡园园[1] 

机构地区：[1]南方医科大学第三附属医院内分泌代谢科,广州510630

出　　处：《国际内分泌代谢杂志》2013年第2期76-80,共5页International Journal of Endocrinology and Metabolism

基　　金：广东省科技计划项目（2009B11400036）

摘　　要：目的探讨糖尿病大鼠肾组织局部血管紧张素转换酶（ACE）2对肾小球足细胞的影响及厄贝沙坦的干预作用。方法56只Wistar大鼠经链脲佐菌素诱导糖尿病模型，死亡9只，其余随机分为糖尿病组（n=11）、30mg/（kg·d）肼屈嗪干预组（n=9）、25mg/（kg·d）厄贝沙坦干预组（n=9）、50mg／（kg·d）厄贝沙坦干预组（n=9）、200mg／（kg·d）厄贝沙坦干预组（n=9），同时设正常对照组（n=7）。于造模后第4周开始予肼屈嗪、厄贝沙坦干预，第12周观察24h尿微量白蛋白排泄率（UAER），采用免疫组化技术检测肾组织ACE2的分布和表达情况，免疫组化SP法检测肾小球WT1表达情况，Image．Pro Plus 6．0彩色图像分析系统半定量检测足细胞密度。结果正常对照组UAER低于糖尿病组和药物干预组[包括肼屈嗪干预组、25mg／（kg·d）厄贝沙坦干预组、50mg／（kg·d）厄贝沙坦干预组、200mg／（kg·d）厄贝沙坦干预组]（P〈0．001）；药物干预组UAER低于糖尿病组（P〈0．001）；所有厄贝沙坦干预组UAER较肼屈嗪干预组显著降低（P〈0．05）；50mg／（kg·d）厄贝沙坦干预组、200mg／（kg·d）厄贝沙坦干预组UAER较25mg／（kg·d）厄贝沙坦干预组明显降低（P〈0．001）。肾组织ACE2表达与肾小球足细胞密度呈正相关（r=0．381，P〈0．001），糖尿病组ACE2表达较正常对照组明显降低（P〈0．05），而所有厄贝沙坦干预组显著高于糖尿病组和肼屈嗪干预组（P〈0．001），厄贝沙坦干预组、肼屈嗪干预组足细胞密度显著高于糖尿病组（P〈0．001）；200mg／（kg·d）厄贝沙坦干预组高于肼屈嗪干预组、25mg／（kg·d）厄贝沙坦干预组、50mg／（kg·d）厄贝沙坦干预组、糖尿病组。结论肾组织ACE2减少可导致足细胞密度降低，进而引起肾脏损害；而厄贝沙坦可上调肾组织ACE2的表达，增加足细胞密度，发挥降压外的肾�Objective To observe the effects of the renal local angiotensin-converting enzyme 2 （ACE2） expressions on glomerular podocytes in diabetic rat and the flmction of irbesartan. Methods Fifty-six Wistar rats were induced diabetes by streptozotocin, nine were dead. The others were randomly divided into diabetes group （ n = 11 ）, hydralazine administrated group （ n = 9 ）, 25 mg· kg^-1· d^-1 irbesartan administrated group（n =9）,50 mg· kg^-1· d^-1 irbesartan administrated group（n =9）,and 200mg· kg^-1· d^-1 irbesartan administrated group （n = 9）, meanwhile normal control group were established （n = 7 ）. Four weeks after modeling,rats were administered with hydralazine or irbesartan separately. In the 12th week, 24 hour urinary albumin excretion rate （UEAR）was measured. The distribution and expression of ACE2 in renal tissue were detected by immunohistochemistry. The renal glomemlus WT1 expression was detected by streptavidin- perosidase（ SP ）. Podocytes density was detected by Image. Pro Plus 6. 0. Results The UAER in normal control group was lower than that in diabetes group and all the drug intervention groups （ including hydralazine administrated group, 25 mg· kg^-1· d^-1 irbesartan administrated group, 50 mg· kg^-1· d^-1 irbesartan administrated group, and 200 mg· kg^-1· d^-1 irbesartan administrated group ） （ P 〈 0. 001 ）. The UAER in all the drug intervention groups were lower than that in diabetes group （P 〈 0. 001 ）. And in all the irbesartan administrated groups UAER were lower than that in hydralazine administrated group （ P 〈 0.0 5 ） . In 50 mg· kg^-1· d^-1 irbesartan administrated group and 200mg· kg^-1· d^-1 irbesartan administrated group, UAER were lower than that in 50 mg· kg^-1· d^-1 irbesartan administrated group（P 〈0.001 ）. The level of renal ACE2 was positively correlated with podoeytes density（ r =0. 381 ,P 〈0. 001 ）. And it was significantly lower in diabetes group than that in normal control group（P 〈0. 05）

关 键 词：糖尿病 肾小球足细胞 血管紧张素转换酶2 尿微量白蛋白排泄率 

分 类 号：R544.1[医药卫生—心血管疾病]