摘要
目的探讨糖尿病心肌病变发生的机制。方法将16只雄性Wistar大鼠随机分为对照组和观察组各8只,观察组腹腔注射链脲佐菌素(STZ)建立糖尿病模型。喂养4周后处死大鼠,取心脏称重,计算心脏质量指数;测定血清基质金属蛋白酶-2(MMP-2)及其抑制物TIMP-2含量,心肌组织MMP-2活性、TIMP-2蛋白、MMP-2mRNA和TIMP-2 mRNA表达;VG染色观察心肌胶原容积分数(CVF)变化。结果与对照组比较,实验4周时观察组心脏质量、体质量显著下降,心脏质量指数升高,血清TIMP-2显著升高,心肌MMP-2活性和mRNA表达明显减弱,TIMP-2 mRNA表达显著增强,心肌CVF明显升高;相关分析表明CVF与心肌MMP-2活性、mRNA表达呈明显负相关,而与TIMP-2 mRNA表达呈明显正相关。结论糖尿病心肌组织中MMP-2活性和mRNA表达显著减弱、TIMP-2表达明显增强,其与间质胶原蓄积密切相关,是糖尿病心肌间质重构的重要原因之一;血清TIMP-2水平与心肌表达一致,可作为糖尿病心肌病早期预测和病情监测的指标之一。
[ Objective ] To observe the changes of MMP-2/TIMP-2 in the hearts of streptozotocin-induced diabetic rats and gain insight into their roles in ECM remodeling on an experimental animal model of diabetic cardiomyopathy. [ Methods] 16 male Wistar rats were randomly divided into two groups： normal control group and diabetic rats group. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. At the end of 4 weeks, serum MMP-2 and TIMP- 2 levels were examined by enzyme linked immunosorbent assay （ELISA）. Cardiac MMP-2 activity was detected by gel zymography. TIMP-2 protein expression was analyzed by immunohistochemistry. MMP-2 and TIMP-2 gene expressions were measured by reverse transcription pelymerase chain reaction （RT-PCR）, Cardiac collagen contents were analyzed by Van Gieson （VG） staining and the results were quantified by densitometry. [ Results] Diabetes mellitus was associated with a decreased body weight and heart weight hut an increased HW/BW. In the diabetic group, serum MMP-2 levels had a tendency to increase hut not significantly, while serum TIMP-2 significantly increased. Both the activity and expression of MMP-2 decreased in the hearts of diabetic rats. TIMP-2 gene expression in myocardium increased significantly. VG staining showed a marked deposition of collagen in diabetic group. Multivariate analysis revealed that total collagen contents correlated negatively with the activity and gene expression of MMP-2 in the myocardium, and correlated positively with TIMP-1 mRNA expression. [ Conclusions] The decrease in MMP-2 activity and expression and increase in TIMP-2 expression in the myocardium of diabetic rats may lead to impairment of collagen degradation and contribute to the matrix deposition in diabetic myocardiopathy. The correlation between the serum level and cardiac expression of TIMP-2 in diabetic rats suggests that serum TIMP-2 level may be a viable marker for early diagnosis of diabetic myocardiopathy.
出处
《山东医药》
CAS
北大核心
2007年第35期10-13,共4页
Shandong Medical Journal
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。
