氯沙坦对糖尿病大鼠肾脏细胞凋亡及bax/bcl-2表达的影响  

Effects of losartan on apoptosis and expression of bax and bcl-2 in the kidney of diabetic rats

作　　者：张艳玲[1] 段惠军[1] 史永红[1] 李英敏[1] 李英[1] 顾连方[1] 

机构地区：[1]河北医科大学病理教研室,石家庄050017

出　　处：《肾脏病与透析肾移植杂志》2001年第5期411-416,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：教育部归国博士科研基金资助

摘　　要：目的 :探讨血管紧张素受体 1拮抗剂 (AT1Ra)对糖尿病肾脏细胞凋亡及凋亡相关基因的影响。　 方法 :单侧肾切除大鼠腹腔注射STZ诱发糖尿病模型 ,每日灌胃给予AT1Ra氯沙坦 ( 4 0mg/kg) ,共 12周。采用原位末端标记法检测肾脏细胞凋亡情况 ,流式细胞术和免疫组化检测肾皮质Bax和Bcl 2表达 ,原位杂交检测bax和bcl 2mRNA表达。　 结果 :糖尿病组较对照组肾小球、肾小管凋亡细胞数明显增多 ,bax和bcl 2蛋白及mRNA表达增强 ,Bax/Bcl 2增高 ;氯沙坦治疗组较糖尿病组凋亡细胞数减少 ,bax表达减弱 ,bcl 2表达增强 ,Bax/Bcl 2降低。　 结论 :氯沙坦可能通过影响凋亡相关基因bax和bcl 2表达而抑制肾脏细胞凋亡 ,从而发挥肾脏保护作用。Objective:To investigate the effects of losartan on apoptosis and the expression of bax and bcl 2 in the kidney of diabetic rats. Methodology:Diabetes was induced in uninephrectomized SD rats by intraperitoneal injection of STZ(65 mg/kg ).Losartan(40mg/kg)was administered daily by gavage from the next day of the induction to diabetes for 12 weeks.Apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated d UTP nick end labeling (TUNEL).Flow cytometry,immunohistochemistry and in situ hybridyzation were used to detect the protein and mRNA expression of bax and bcl 2. Results:Compared with the control kidney in uninephrectomized rats without losartan treatment,the apoptotic cells were more in number and the expression of bax and bcl 2 heavier in density( P <0 05)with an increased ratio of bax/bcl 2 in the diabetic kidneys.After losartan treatment,decrements were found in the number of apoptotic cells,the expression of bax,and the ratio of bax/bcl 2,while an increment of the expression of bcl 2 was noticed. Conclusion:Inhibition of apoptosis and regulation of bax/bcl 2 expression may be responsible for the renal protective effects of losartan in uninephrectomized SD rats.

关 键 词：血管紧张素受体1拮抗剂 糖尿病肾病 细胞凋亡 

分 类 号：R965[医药卫生—药理学]