中药降糖三黄片干预糖尿病心肌病大鼠心室重构的作用机制

目的观察糖尿病心肌病大鼠胞浆胞外调节蛋白激酶1/2(ERK1/2)的表达及中药降糖三黄片对其影响,进一步探讨降糖三黄片改善糖尿病心肌病大鼠心室重构的作用机制。方法 49只清洁级Wistar大鼠以高脂高热量饮食诱导加小剂量链脲佐菌素(30 mg·kg-1)注射建立2型糖尿病心肌病动物模型,随机分为正常组、模型组、中药组和西药组。中药组给予降糖三黄片,剂量为787.5 mg·kg-1·d-1;西药组给予卡托普利,剂量为4 mg·kg-1·d-1;正常组及模型组灌服等量蒸馏水;均灌胃治疗8周。实验末腹主动脉采血检测各组空腹血糖、胆固醇和甘油三酯以及胰岛素水平;超声心动仪评价各组大鼠心脏的结构和功能,摘取心脏测质量,计算左心室质量指数;免疫组织化学法检测心肌细胞胞浆ERK1/2的含量。结果中药组血糖、血脂水平明显下降,胰岛素敏感指数上升,同模型组和西药组比较差别有统计学意义(P<0.05)。中药降糖三黄片能够改善超声心动图监测的心功能各项指标,降低左心室质量指数,其作用与西药卡托普利(西药组)相似,2组比较差别无统计学意义(P>0.05)。模型组心肌细胞胞浆ERK1/2水平明显高于正常组,差别有统计学意义(P<0.05);中药组和西药组心肌细胞胞浆ERK1/2水平与模型组比较明显下降,差别有统计学意义(P<0.05);中药组和西药组比较,心肌细胞胞浆ERK1/2水平差别无统计学意义(P>0.05)。结论降糖三黄片能有效改善糖尿病心肌病大鼠的心室重构,其效果与西药卡托普利相似,其改善糖尿病心肌病大鼠心室重构的作用机制可能与抑制ERK1/2的表达有关。

Mechanism of Jiangtangsanhuang tablet in interference the cardiac remodeling of diabetic cardiomyopathy rats

Objective To observe the affection of Jiangtangsanhuang tablet on the expression of extracellular signal-regulated kinase（ERK1/2）of rats with diabetic cardiomyopathy（DCM）,furthermore to explore the mechanism of Jiangtangsanhuang tablet in improving the cardiac remodeling of DCM rats. Methods Forty-nine Wistar rats were fed with high cholesterol diet throughout the study period,streptozocin（30 mg·kg-1）was given to establish the DCM model.And the rats were divided into control group,model group,Chinese medicine group and western medicine group,respectively.Chinese medicine group was given Jiangtangsanhuang tablet with the dose of 787.5 mg·kg-1·d-1;western medicine group was given captopril with the dose of 4 mg·kg-1·d-1;control group and model group were given distilled water;the periodicity was 8 weeks.At the end of the experiment,blood from abdominal aorta was collected,and fasting blood glucose（FBG）,cholesterol,triglyceride,insulin level were detected.Left ventricular function was determined by echocardiography.Then the rats were sacrificed,left ventricular weight index were calculated;the ERK1/2 contents in myocardial cell were detected by immunohistochemical method. Results Compared with model group and western group,the levels of blood sugar and blood fat decreased,insulin sensitivity index（ISI） increased（P0.05）.Cardiac function was significantly improved in Chinese medicine group,the effect was similar with captopril,there was no statistically significant between two groups（P0.05）.Compared with control group,the ERK1/2 level in cardiomyopathy was higher in model group（P0.05）.In Chinese medicine group and western medicine group,the ERK1/2 levels in cardiomyopathy were lower than model group（P0.05）.There was no statistically significant in ERK1/2 levels between Chinese medicine group and western medicine group（P0.05）. Conclusion Jiangtangsanhuang tablet can significantly improve the cardiac function and left ventricular remodeling,the overall curative effects was similar with captopril,and the inhibition of ERK1/2 expression may be one of the mechanisms.