厄贝沙坦对糖尿病大鼠肾组织MMP-2、TIMP-2和Ⅳ-C表达的影响

目的:观察基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)和Ⅳ型胶原(Ⅳ-C)在糖尿病大鼠肾组织中的表达及厄贝沙坦干预后的影响。方法:30只♂SD大鼠随机分为3组:正常对照组(NC组)、糖尿病模型组(DM组)、糖尿病模型+厄贝沙坦(50mg·kg-1)组(DI组)。后2组腹腔注射链脲佐菌素诱导大鼠建立糖尿病模型后DI组灌胃厄贝沙坦。8周后,用免疫组化方法(SP法)和逆转录-聚合酶链反应法(RT-PCR)检测各组大鼠肾皮质MMP-2、TIMP-2及Ⅳ-C的表达。结果:与NC组比较,DM组大鼠肾小球MMP-2蛋白、mRNA的表达明显降低,TIMP-2及Ⅳ-C蛋白、mRNA明显增强(P<0.01),出现糖尿病肾病典型的病理改变。与DM组比较,DI组MMP-2蛋白、mRNA表达明显增强(P<0.01),TIMP-2和Ⅳ-C表达明显降低(P<0.01)。结论:厄贝沙坦可能通过调节MMP-2/TIMP-2的平衡,减少细胞外基质Ⅳ-C积聚而发挥对糖尿病大鼠的肾脏保护作用。

Effects of lrbesartan on Expression of MMP-2, TIMP-2 and Ⅳ-C in Kidney of Diabetic Rats

OBJECTIVE： To investigate the expression of matrix metallopro teinase-2 （MMP-2）, tissue inhibitor of metallo- proteinase-2 （TIMP-2） and collagen Ⅳ （Ⅳ-C） in kidney of diabetic rats and the intervention effect of irbesartan. METHODS： 30 male SD rats were randomly divided into three groups： normal control group （NC group）, diabetes mellitus group （DM group） and diabetes mellitus＋50 mg·kg^-1 irbesartan group （DI group）. DM and DI group were injected with streptozocin intraperitoneally to reduce diabetic model. After 8 weeks the expression of MMP-2, TIMP-2 and IV-C in kidney tissure were determined by immunohistochemistry method （SP） and RT-PCR. RESULTS： Compared with NC group, DM group showed the expression of protein and mRNA of MMP-2 significantly reduced while that of TIMP-2 and IV-C increased （P〈0.01）. The pathologic changes of diabetic nephropathy occurred in DM group. In D1 group the expression of protein and mRNA of MMP-2 increased significantly while that of TIMP-2 and IV-C （P〈0.01） decreased, as compared with DM group. CONCLUSION： Irbesartan may regulate the balnce of MMP-2 and TIMP-2 and weaken the accumulation of Ⅳ-C to protect kidney of rats.