厄贝沙坦对糖尿病大鼠肾组织MMP-9、TIMP-1表达的影响

[目的]观察厄贝沙坦对糖尿病(DM)大鼠肾脏病变的保护作用及其机制。[方法]建立STZ诱导的糖尿病SD大鼠模型,随机分成3组:正常对照组、DM模型组、厄贝沙坦治疗组。各组大鼠采用相应的干预措施处理12周。常规方法检测各组大鼠肾重/体重、血糖、尿素氮、血肌酐、尿白蛋白排泄率(UAER),免疫组化法检测肾组织MMP-9、TIMP-1表达,透射电镜观察肾脏超微结构。[结果]DM模型组大鼠肾组织MMP-9的表达较正常对照组明显下调(P﹤0.O1),经厄贝沙坦治疗后的厄贝沙坦治疗组表达明显上调(P﹤0.01),但仍低于正常对照组(P﹤0.01);DM模型组大鼠肾组织TIMP-1的表达较正常对照组明显上调(P﹤0.01),经厄贝沙坦治疗后的厄贝沙坦治疗组表达明显下调(P﹤0.01),但仍高于正常对照组(P﹤0.01)。血糖、UAER、尿素氮、血肌酐、肾重/体重等厄贝沙坦治疗组指标值较DM模型组有所下降(P﹤0.01)。[结论]MMP-9、TIMP-l的表达变化与肾小球细胞外基质(ECM)降解减少相关,可能促进了糖尿病肾病的发生,厄贝沙坦可能通过干预这种表达变化减缓糖尿病肾病的发生和发展。

EFFECT OF IRBESARTAN ON THE EXPRESSION OF MMP-9,TIMP-1 IN KIDNEY TISSUES OF DIABETES MELLITUS RATS

[Objective]To investigate the protective effects of Irbesartan on renal lesion in diabetic rats.[Methods]The diabetic SD rats were induced by STZ,divided into three groups:normal control group,diabetic control group and Irbesartan group.After experimental rats in every group were respectively treated for 12 weeks by above intervention methods.The relative kidney weight,blood sugar,urea nitrogen,serum creatinine,and urinary albumin excretion rate(UAER)were detected by normal methods,MMP-9 and TIMP-1 in renal tissue were respectively detected by immunohistochemical techniques,and ultramicrostructure of kidney was observed by transmission electron microscope.[Results]Compared with normal control group,the expressions of MMP-9 were decreased in diabetic control group(P﹤0.01).The expressions of MMP-9 in Irbesartan group were higher than those in diabetic control group(P﹤0.01),but they were still lower than those in normal control group(P﹤0.01).Compared with normal control group,the expression of TIMP-1 was increased in diabetic control group(P﹤0.01).The expression of TIMP-1 in Irbesartan group were lower than those in diabetic control group(P﹤0.01),but they were still higher than that in normal control group(P﹤0.01).The ultramicrostructure of kidney was noticeably changed,and the blood sugar,UAER,urea nitrogen,serum creatinine,and relative kidney weight were significantly increased in diabetic rats.While the above indexes in group Irbesartan group was significantly lower than in diabetic control group(P﹤0.01).[Conclusion]The changes of the expressions of MMP-9 and TIMP-1 decrease the degradation extracellular matrix,which promote the occurrence and progress of diabetic nephropathy.Irbesartan may attenuate the occurrence and progress of diabetic nephropathy through intervening this change.