黄连-肉桂配比对慢性心力衰竭大鼠下丘脑-垂体-肾上腺轴的影响

Effect of proportions of Huanglian Rougui ratio in rats with chronic heart failure based on hypothalamic-pituitary-adrenal axis

目的:探讨黄连-肉桂不同配比对慢性心力衰竭大鼠下丘脑-垂体-肾上腺轴的干预机制。方法:将60只大鼠分为空白组、模型组、黄连组、肉桂组、黄连-肉桂组。心脏超声测量左室射血分数(LVEF)、左室内径缩短率(LVFS)。酶联免疫吸附(ELISA)法检测大鼠血清N端脑钠肽前体(NT-proBNP)水平,判断造模成功与否。给药4周后,HE染色观察大鼠心肌组织形态变化,ELISA检测促肾上腺皮质激素(ACTH)、肾上腺皮质酮(CORT)、促肾上腺皮质激素释放激素(CRH)表达。Western blotting法检测葡萄糖转运蛋白4(GLUT4)的表达。结果:模型组大鼠心肌细胞广泛排列紊乱,细胞轮廓不清晰,间隙增大,可见部分细胞空泡变性。模型组大鼠NT-proBNP、ACTH、CORT、CRH表达高于空白组,LVEF、LVFS、GLUT4低于空白组(均P<0.01)。黄连组、肉桂组、黄连-肉桂组的NT-proBNP低于模型组(均P<0.01)。黄连-肉桂组的ACTH、CORT表达低于模型组,GLUT4蛋白表达高于模型组(均P<0.01)。结论:黄连-肉桂配伍可改善心衰大鼠症状,降低血清NT-proBNP水平,其保护心功能的机制可能与调控下丘脑-垂体-肾上腺轴及胰岛素抵抗相关,黄连-肉桂最佳配比为10∶1。

Objective:To explore intervention mechanism of different proportions of Huanglian Rougui ratio on rats with chronic heart failure by interfering with hypothalamus-pituitary-adrenal axis.Methods:Sixty rats were divided into blank group,model group,Huanglian group,Rougui group,Huanglian-Rougui group.Left ventricular ejection fraction(LVEF),left ventricular diameter shortening(LVFS)were measured by echocardiography.Serum N-terminal pro-brain natriuretic peptide(NT-proBNP)levels were measured by enzyme-linked immunosorbent assay(ELISA)to judge the success of the mold.Four weeks after administration,the morphological changes of myocardial tissue were observed by HE staining.Corticotropin(ACTH),corticosterone(CORT)and corticotropin-releasing hormone(CRH)were detected by ELISA.The expression of glucose transporter 4(GLUT4)protein was detected by Western blotting.Results:The cardiomyocytes of the model group were widely arranged in disorder,the outline of the cells not clear,gap enlarged,and some vacuolar degeneration could be seen.The expressions of NT-proBNP,ACTH,CORT and CRH in model group were higher than those in the blank group,while LVEF,LVFS and GLUT4 were lower than those in the blank group(all P<0.01).The NT-proBNP of Huanglian group,Rougui group and Huanglian-Rougui group were lower than those in the model group(all P<0.01).The expression of ACTH and CORT in Huanglian-Rougui groups were lower than those in the model group,and GLUT4 protein expression was higher than that in model group(all P<0.01).Conclusion:Huanglian-Rougui combination can improve the symptoms of heart failure rats and reduce the level of serum NT-proBNP.The mechanism of protecting cardiac function may be related to regulation of hypothalamic-pituitary-adrenal axis and insulin resistance.The optimum ratio of Huanglian Rougui was 10∶1.