降糖消渴颗粒对实验性糖尿病大鼠心肌MAPK信号通路影响

摘要

Objective:To explore the effect of Jiangtang Xiaoke granule (JTXKG) on pathological changes and MAPK signal pathway in myocardial tissues of experimental diabetic rats.Methods:Diabetic rats were induced by high-fat diet and low dose streptozotocin (30 mg.kg-1).JTXK granule 9 g/kg (based on crude herb equivalent) and pioglitazone 5 mg/kg (as a positive control for comparison) were orally administrated to diabetic rats for 4 weeks.The ratio of heart weight to body weight and the pathological changes of myocardial tissues were measured.In addition,the protein expression levels of MEK1/2,p38 MAPK,phosphate-p38 MAPK in myocardial tissues were detected.Results:JTXKG reduced the ratio of heart weight to body weight.Results of HE-staining showed that JTXKG improved pathological changes of myocardial tissues.Moreover,JTXKG significantly down-regulated protein levels of MEK1/2,p38 MAPK,phosphate-p38 MAPK in myocardial tissues of the diabetic rats.Conclusion:JTXKG could protect the rats from diabetic cardiomyopathy by inhibiting the MAPK signal pathway in the myocardial tissues of diabetic rats.%目的:观察降糖消渴颗粒对实验性糖尿病大鼠心肌病理形态及丝裂原活化蛋白激酶(MAPK)信号通路的影响,研究其对糖尿病心肌病的作用及机制.方法:SD大鼠高脂饲料喂养4周后结合腹腔注射链脲佐菌素(STZ) 30 mg/kg,建立2型糖尿病大鼠模型,将成模的大鼠按血糖随机分为模型组、阳性对照组(吡格列酮片1.5 mg/kg BW)、降糖消渴颗粒组(9g生药/kg BW),并设正常对照组.干预4周后,检测各组大鼠心脏质量指数;心肌组织切片并用HE染色,观察药物对糖尿病大鼠心肌组织病理形态的影响;应用western-blot法检测心肌MEK1/2,p38 MAPK,p-p38 MAPK的蛋白表达情况.结果:降糖消渴颗粒组大鼠心脏质量指数明显低于模型组(P＜0.05),降糖消渴颗粒对实验性糖尿病大鼠心肌组织的病理改变有改善作用,同时能下调糖尿病大鼠心肌组织MEK1/2,p38 MAPK总蛋白表达,且能减少p-p38 MAPK蛋白量(P＜0.05),提示其对糖尿病大鼠心肌MAPK信号通路具有抑制作用.结论:降糖消渴颗粒能够通过调节心肌组织MAPK信号通路,改善心肌纤维化及心肌细胞凋亡,从而实现延缓糖尿病心肌病进展的作用.