苯那普利对糖尿病大鼠肾皮质MMP-2、TIMP-2和C-IV表达的影响  

Effects of Benazepril on Expression of Matrix Metalloproteinase-2,Tissue Inhibitor of Metalloproteinase-2 and Collagen IV in Renal Cortex of Diabetic Rats

作　　者：毛春谱[1] 李小毅[1] 张红梅[1] 林桂芬[1] 

机构地区：[1]苏州大学附属第四医院内分泌科,江苏无锡214062

出　　处：《苏州大学学报（医学版）》2009年第4期632-635,F0003,共5页Suzhou University Journal of Medical Science

摘　　要：目的探讨苯那普利对糖尿病大鼠肾皮质中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)和IV型胶原(C-IV)表达水平的影响。方法40只雄性SD大鼠随机分为3组:正常对照组(C组),糖尿病未治疗组(DM组),糖尿病苯那普利(10mg/kg)治疗组(DB组)。8周后,用免疫组化方法(SP法)和RT-PCR方法检测各组大鼠肾皮质MMP-2、TIMP-2及C-IV的表达。结果DM组大鼠肾小球MMP-2蛋白、mRNA的表达较C组明显降低,TIMP-2及C-IV蛋白、mRNA明显升高,差异有高度统计学意义(P<0.01),出现糖尿病肾病(DN)典型的病理改变。DB组MMP-2蛋白、mRNA较DM组表达明显升高(P<0.01)、TIMP-2和C-IV表达较DM组明显降低(P<0.01),病理改变好转。结论苯那普利可能通过逆转糖尿病大鼠肾皮质MMP-2、TIMP-2的表达,降低C-IV的堆积,对糖尿病肾病(DN)起保护作用。Objective To investigate the effects of benazepril on expressions of matrix metallopro teinase-2, tissue inhibitor of metalloproteinase-2 and collagen IV （C-IV） in the kidney of diabetic rats. Methods Forty Sprague-Damly rats were randomly divided into three groups： the control group （C group）, diabetes mellitus group （DM group） and diabetic group treated with benazepril （10mg/kg）（DB group）. Eight weeks later, expression of MMP-2, TIMP-2 and C-IV in the kidney fissure was determined by immunohistochemistry method （SP）and RT-PCR. Results Compared with C group, expressions of protein and mRNA MMP-2 significantly reduced in the glomeruli,while expressions TIMP-2 and C-IV were increased in the DM group （P〈0.01）. Meanwhile, the pathologic changes of the glomeruli were seri- ous in DM group. The abnormal expressions of these proteins, mRNA and pathologic changes were dra- matically improved in diabetic rats by benazepril treatment （P〈0.OI）. Conclusion Benazepril can exert protective effects on diabetic nephropathy, partly through upregulating MMP-2 and decreasing TIMP-2, C-IV accumulation in renal cortex.

关 键 词：苯那普利 糖尿病肾病 基质金属蛋白酶-2 基质金属蛋白酶抑制因子-2 IV型胶原 

分 类 号：R587.2[医药卫生—内分泌]