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

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。

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

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.