罗格列酮对糖尿病大鼠心肌纤维化及炎症因子表达的影响

Effect of rosiglitazone on the myocardial interstitial fibrosis and cytokines expression of diabetic rats

目的探讨盐酸罗格列酮(RGZ)对糖尿病(DM)大鼠心肌纤维化及炎症因子表达的影响。方法 30只实验大鼠分正常对照(NC)组(n=8)、DM组(n=11)、RGZ组(n=11),用药12周。测血糖、体重、HbA_1c、心脏重量、左室心肌胶原含量、血清单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子α(TNF-α)水平、心肌结缔组织生长因子(CTGF)表达的变化,观察心肌细胞超微结构。结果与NC组相比,DM组大鼠左室心肌组织胶原含量明显升高(16%±2% vs 10%±3%,P<0.01),存在心肌间质纤维化;DM组MCP-1、TNF-α水平、心肌CTGF表达明显升高(分别为34.2±3.9 vs 17.5±2.8,9.8±2.5 vs 5.0±1.4,154±19 vs 98±16,P均<0.01);RGZ治疗后,左室心肌组织胶原明显下降(12%±3% vs 16%±2%,P<0.05),MCP-1、TNF-α水平及心肌CTGF表达明显降低(分别为20.2±3.2 vs 34.2±3.9,P<0.01;6.5±2.1 vs 9.8±2.5,P<0.01;121±16 vs 154±19,P<0.05)。结论 RGZ能明显抑制DM大鼠心肌间质纤维化,并能降低MCP-1、TNF-α水平及心肌CTGF的蛋白表达。

Objective To investigate the effect of rosiglitazone on the myocardial interstitial fibrosis,the serum levels of MCP-1 and TNF-α and connective tissue growth factor（CTGF） expression in myocardium of diabetic rats. Methods Diabetic rats were induced by streptozotocin. Thirty male Sprague-Dawley rats were randomly divided into 3 groups： diabetic group （DM group, n =11 ）, rosiglitazone-treated DM group （R group, n = 11） and control group （C group, n = 8）. After 12-week treatment, blood glucose, weight, HbAlc and heart weight were detected respectively. By electron microscopy we observed the changes of myocardial ultrastructure. The serum levels of MCP-1 and TNF-α were quantified by ELISA. Western blot was used to detect the protein expression of CTGF. Results By the end of the experiment, there was no significant differences in fasting blood glucose between DM group and rosiglitazone group. However, compared with DM group, the heart/body weight index of rosiglitazone group was significantly lower（0. 37±0. 07 vs 0. 45±0. 07, P（O. 05）. The collagen content of rosiglitazone group （12% ±3%） was significantly lower than that of the DM group（16% ±2%, P（ 0.05）. The levels of MCP-1 and TNF-α in serum were significantly lower in the rosiglitazone group than in DM group （20.2±3.2 vs 34.2±3.9,P〈0.01;6.5±2.1 vs 9.8±2.5,P（0.01）. The value of protein expression of CTGF was significantly lower in the rosiglitazone group than in DM group （121±16 vs 154±19, P（0. 05）. Conclusions Rosiglitazone decreases the serum levels of MCP-1 and TNF-α and inhibits the protein expression of CTGF, which may play an important role in the process of ameliorating myocardial interstitial fibrosis in diabetic rats.