2型糖尿病大鼠心脏MMP-2、MMP-9、TIMP-1、TIMP-2的变化与糖尿病心肌病变关系

目的 探讨2型糖尿病（T2DM）大鼠心脏基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）、基质金属蛋白酶组织抑制物1（TIMP-1）、基质金属蛋白酶组织抑制物2（TIMP-2）的变化及其在糖尿病心肌病变（Diabetic Cardiomyopathy,DC）发病中的意义.方法 高脂食物喂养、小剂量链脲菌素诱导2型糖尿病大鼠模型.正糖高胰岛素嵌铗技术（EICT）检测两组大鼠胰岛素抵抗情况,葡萄糖输注速率（GIR）表示胰岛素抵抗;测定大鼠体重（BW）、心脏重量（HW）和计算HW /BW;RT-PCR测定两组大鼠MMP-2、MMP-9、TIMP-1、TIMP-2的mRNA水平,免疫组化法检测MMP-2、MMP-9、TIMP-1、TIMP-2和Ⅰ、Ⅲ胶原蛋白水平.结果 糖尿病大鼠GIR明显低于正常对照组（P〈0.01） .糖尿病大鼠心脏：HW和HW /BW明显高于正常对照组（P〈0.05）,Ⅰ、Ⅲ型胶原明显增多（P〈0.01）,MMP-2、TIMP-1、TIMP-2的mRNA表达增加（P〈0.01）, MMP-2、MMP-9、TIMP-1、TIMP-2的蛋白含量增加（MMP-2、TIMP-1：P 〈0.05;TIMP-2：P〈0.01）;MMP-2、MMP-9与TIMP-1蛋白水平比值及MMP-2与TIMP-2蛋白水平比值均显著降低.结论 T2DM大鼠心脏MMP-2、MMP-9、TIMP-1、TIMP-2增加,MMPs/TIMPs比值降低,心脏Ⅰ、Ⅲ型胶原明显增多;心脏MMPs/TIMPs表达改变与心脏间质纤维化有关.

Study on the relationship between MMP -2 ,MMP -9 ,TIMP - 1 ,TIMP -2 and the diabetic myocardium damage in 2 diabetes rats

Objective To explore the role of MMP -2 ,MMP -9 ,TIMP - 1 ,TIMP -2 alterations in the pathogenesis of diabetic cardiomyopathy in type 2 diabetes （ T2DM ） rats. Methods Sixteen male Wistar rats were randomly divided into normal control group and T2DM group, each had 8 rats. T2DM rats were induced by small dose injection of streptozoteein and being fed with high - fat - diet. The body weight（BW） , heart weight（HW） and HW/BW were measured. The mRNA expression of MMP - 2, MMP - 9, TIMP - 1, TIMP - 2 were determined by RT - PCR. The protein level of MMP - 2, MMP - 9, TIMP - 1, ＇lIMP -2, collagen I and collagen In were detected by immunohistochemistry. Results In the T2DM group, body weight increased as compared with the normal control group （ P 〈 0.01 ）. The mRNA expression of MMP - 2, MMP - 9, TIMP- land TIMP-2 increased significantly（ P 〈0.01 ） ,the protein level of these increased（ MMP- 2, MMP- 9, TIMP- 1： P〈0.05; TIMP-2：P〈0.01）, collagen I and collagen III also increased markedly（P〈0.01）.Conclusion Thechanges of MMPs/TIMPs in the T2DM rats caused imbalance between generation and degradation of collagen I and collagen III, indicating that MMPs/TIMPs may play important role in the pathogenesis of diabetic cardiomyopathy.