糖尿病大鼠心肌胶原代谢的变化及与MMP-2/TIMP-2表达的关系  

Changes of collagen metabolism and MMP-2/TIMP-2 in hearts of diabetic rats

作　　者：李倩[1] 汪翼[1] 孙书珍[1] 陈瑶[1] 王立俊[1] 

机构地区：[1]山东大学附属省立医院儿科,济南250021

出　　处：《山东大学学报（医学版）》2010年第3期1-6,共6页Journal of Shandong University:Health Sciences

基　　金：山东省科技厅资助项目(2002BB1DBA2);山东省自然科学基金资助项目(Y2002C35)

摘　　要：目的探讨不同时期1型糖尿病大鼠心肌间质胶原代谢的动态变化及其与基质金属蛋白酶-2及其抑制剂-2(MMP-2/TIMP-2)表达的关系。方法Wistar大鼠随机分为正常对照4周组和12周组,糖尿病4周组和12周组。糖尿病模型以腹腔注射60mg/kg链脲佐菌素(STZ)诱发建立。喂养4周和12周后测定大鼠心肌胶原含量、MMP-2/TIMP-2血清含量和心肌活性、基因和蛋白表达。结果与同期正常对照组相比,糖尿病组大鼠心肌间质胶原明显增多(P<0.01),MMP-2活性、基因和蛋白表达明显减弱(除DM4周组MMP-2活性P<0.05外,P均<0.01),TIMP-2血清水平和mRNA表达显著升高(P<0.05,P<0.01),且随病程延长进一步加剧。MMP-2血清水平和TIMP-2蛋白表达在病程4周时升高不明显(P>0.05),12周时明显升高(P<0.05,P<0.01)。心肌胶原容积分数与MMP-2、TIMP-2血清水平呈正相关(r=0.565,P<0.01;r=0.415,P<0.05),与MMP-2活性、基因和蛋白表达呈负相关(r=-0.797,-0.704,-0.613;P<0.01),与TIMP-2基因、蛋白表达呈正相关(r=0.609,0.620;P<0.01)。结论糖尿病大鼠存在心肌间质重塑,且随病程延长而加重。MMP-2/TIMP-2表达失衡可能是糖尿病心肌间质重塑的重要原因。血清MMP-2和TIMP-2可作为糖尿病心肌病早期预测的可能指标。Objective To study the dynamic changes of collagen metabolism and MMP-2/TIMP-2 expressions in hearts of diabetic rats.Methods Wistar rats were randomly divided into four groups：4-week normal controls,4-week diabetic rats,12-week normal controls,and 12-week diabetic rats.The diabetic rats were induced by injecting streptozotocin（STZ,60 mg/kg）.The collagen content,serum MMP-2/TIMP-2 levels,cardiac activity,mRNA and protein expressions of MMP-2/TIMP-2 were determined.Results The collagen contents were increased in diabetic rat hearts（P〈0.01）.The activity,mRNA expression and protein level of MMP-2 were decreased（P〈0.01 except P〈0.05 in MMP-2 activity between 4-week diabetic rats vs normal controls） while the serum level and mRNA expression of TIMP-2 were increased（P〈0.05,P〈0.01） in diabetic hearts.The serum MMP-2 level and cardiac TIMP-2 protein level were slightly increased at 4 weeks（P〉0.05） but markedly at 12 weeks（P〈0.05,P〈0.01） in diabetic rats.The cardiac MMP-2/TIMP-2 content was positively related to the serum MMP-2/TIMP-2 levels（r=0.565,P〈0.01;r=0.415,P〈0.05） and gene and protein expressions of TIMP-2（r=0.609,0.620;P〈0.01） while it was negatively related to activity,gene and protein expressions of MMP-2（r=-0.797,-0.704,-0.613;P0.01）.Conclusion Imbalance of MMP-2/TIMP-2 might participate in the development of diabetic cardiomyopathy.Serum MMP-2/TIMP-2 might be potential markers for early diagnosis of diabetic cardiomyopathy.

关 键 词：糖尿病心肌病 胶原 基质金属蛋白酶 金属蛋白酶组织抑制剂 大鼠 WISTAR 

分 类 号：R587.2[医药卫生—内分泌] R-332[医药卫生—内科学]