过氧化物酶体增殖物激活受体γ通路激活对糖尿病大鼠心肌纤维化的影响

Effects of peroxisome proliferator-activated receptor γ signal pathway activation on cardiac fibrosis in diabetic rats

摘要:

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)通路激活对糖尿病大鼠心肌纤维化进展、糖尿病早期心肌重塑和心功能的影响。方法 48只SD大鼠,除正常对照组(Ⅰ组,n=16)外,其余大鼠注射链脲佐菌素制备1型糖尿病大鼠模型后分成2组:糖尿病组(Ⅱ组,n=16)和糖尿病吡格列酮治疗组(Ⅲ组,n=16)。喂养14周后,测定各组大鼠心肌纤维化程度指标;行超声心动图检查及心室内压测定,评价心脏重塑及心功能变化情况。结果 14周后,与Ⅰ组相比,Ⅱ组大鼠心肌羟脯氨酸含量显著升高(P<0.05)。天狼星红染色显示Ⅱ组大鼠心肌弥漫性纤维化较Ⅰ组明显增强;Ⅲ组纤维化程度较Ⅱ组明显减轻。Ⅱ组大鼠左室收缩压显著降低、左室舒张末压显著升高;而Ⅲ组上述情况明显改善。结论吡格列酮干预可减轻糖尿病大鼠心肌纤维化程度,并在一定程度上改善糖尿病早期心脏重塑和心功能状况。

Abstract:

Objective To investigate the effects of peroxisome proliferator-activated receptor γ (PPARγ) signal pathway activation on cardiac fibrosis in diabetic rats,and the effects on cardiac remodeling and cardiac function at early stage of diabetes.Methods Forty-eight SD rats were divided into 3 groups: control,diabetic,and pioglitazone (Piog) treatment groups,with 16 in each group.Except control group,other 32 rats received abdominal injection of streptozotocin (STZ) to prepare type 1 diabetic models.After 14 weeks,fibrosis indices were determined;cardiac remodeling and cardiac function were evaluated by echocardiography and intraventricular pressures indices.Results After 14 weeks,compared with control group,hydroxyproline concentration in diabetic group significantly increased (P<0.05).Sirius red staining showed that cardiac fibrosis was more obvious in diabetic group than in control group,and significantly lessened in Piog group than in diabetic group.In diabetic group,the left ventricular systolic pressure reduced significantly and the left ventricular end-diastolic pressure increased significantly,which were obviously improved by Piog administration.Conclusion Piog treatment can alleviate cardiac fibrosis in diabetic rats and improve cardiac remodeling and cardiac function at early stage of diabetes.