芪苈强心胶囊对慢性心衰大鼠下丘脑室旁核RAS系统及交感神经系统的影响

Effects of Qiliqiangxin on hypothalamic paraventricular nucleus renin angiotensin system and sympathetic nervous system in rats with heart failure

目的观察经侧脑室长期泵入芪苈强心胶囊对慢性心衰大鼠心功能、下丘脑室旁核内肾素-血管紧张素系统(RAS)血管紧张素Ⅱ(AngⅡ)、血管紧张素转换酶(ACE)、血管紧张素Ⅰ型受体(AT_1R)及外周交感神经活性的影响。方法采用结扎冠状动脉左前降支建立急性心肌梗死致心衰模型,造模4周后,经侧脑室插管连接微量注射泵,分别给予醇化芪苈强心溶液和阳性药氯沙坦,给药4周后,应用超声心动图测定各组大鼠心功能变化,HE染色观察心肌组织形态,酶联免疫法测定血浆去甲肾上腺素(NE)、血清N端前脑钠肽(NT-proBNP)及室旁核内AngⅡ含量变化,Real-time PCR和Western blot方法测定室旁核ACE、AT_1R mRNA及蛋白表达水平,PowerLab多通道生理记录仪测定各组肾交感神经活性的变化。结果与假手术组比较,模型组大鼠心功能明显降低,下丘脑室旁核内AngⅡ、ACE、AT_1R表达水平及NE、NT-proBNP表达水平明显升高,肾交感神经放电活性增强;与模型组比较,各给药组均可不同程度改善心衰大鼠心功能,减轻心肌组织形态改变,降低下丘脑室旁核AngⅡ、ACE、AT_1R及NE、NT-proBNP表达水平,降低肾交感神经放电活性。结论经侧脑室连接微量注射泵给予芪苈强心胶囊可降低下丘脑室旁核内RAS系统的激活,降低肾交感神经的活性,改善慢性心衰大鼠心功能,延缓心衰的进展。

Aim To determine the effects of Qiliqiangxin injected into lateral ventricle on Cardiac function,angiotensin Ⅱ( Ang Ⅱ),angiotensin converting enzyme( ACE),angiotensin type 1 receptor( AT_1R) and the sympathetic nervous system in the hypothalamic paraventricular nucleus of rats with chronic heart failure.Methods Rat model of heart failure was prepared by acute myocardial infarction that was induced by ligation of the left anterior descending coronary artery. Four weeks after heart failure, Qiliqiangxin and Losartan were continuously administered via a syringe pump injector connected to lateral ventricle. After four weeks,echocardiogram was used to evaluate the cardiac function and HE was used to observe myocardial tissue morphology,and enzyme linked immunosorbent assay was used to measure plasma norepinephrine( NE),serum NT-proBNP and Ang Ⅱ in the paraventricular nucleus. The expression of ACE and AT_1R at mRNA and protein levels in the paraventricular nucleus was determined by Real-time PCR and Western blot,and the RSNA was measured by Power Lab in anesthetized rats.Results Compared with the sham control,the cardiac function was significantly lower while the Ang Ⅱ,ACE,AT_1R expression in the paraventricular nucleus and RSNA were significantly increased in rats with heart failure. Compared with heart failure control,Qiliqiangxin and Losartan decreased the RSNA and the Ang Ⅱ,ACE,AT_1R expression in the paraventricular nucleus.Conclusion Giving traditional Chinese medicine to the lateral ventricles can decrease the activation of the RAS system,reduce the renal sympathetic nerve activity and improve cardiac function.