心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体的变化对交感神经活动的影响  

The change of angiotensin type 1 receptor in paraventricular nucleus contribute to sympathoexcitation in heart failure

作　　者：孙要军[1] 董华[2] 和荣丽[1] 许艳艳[1] 齐杰[1] 康玉明[1] 

机构地区：[1]山西医科大学基础医学院生理系,太原030001 [2]太原市太航医院影像科

出　　处：《中国药物与临床》2011年第9期993-997,共5页Chinese Remedies & Clinics

基　　金：国家教育部博士点基金(20101417110002;20070114002)

摘　　要：目的观察心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体(AT1-R)可能发生的改变及其对交感神经活动的影响。方法选取雄性SD大鼠,首先进行室旁核插管术,1周后采用左侧冠状动脉结扎术建立大鼠心力衰竭模型或假手术模型,同时各组大鼠分别经微型渗透泵通过室旁核插管持续给予AT1-R阻滞剂缬沙坦(VAL)0.05μg/h或人工脑脊液(aCSF)0.11μl/h干预。4周后检测心功能;电生理记录肾交感神经放电;计算肺/体质量比(L/BW)和右心室/体质量比(RVW/BW);测定血浆去甲肾上腺素(NE)和血管紧张素Ⅱ(AngⅡ)含量;Western blot技术检测下丘脑室旁核内Fra-like和AT1-R蛋白表达情况。结果与假手术组比较,冠状动脉结扎术后4周大鼠的心功能明显降低;血浆NE和AngⅡ浓度增高(P<0.05);肾交感神经放电明显增强;室旁核内Fra-like和AT1-R蛋白表达增加(P<0.05)。与人工脑脊液治疗组比较,接受缬沙坦治疗的心力衰竭大鼠心功能有所改善,外周血NE和AngⅡ含量下降(P<0.05),肾交感神经放电减少(P<0.05),室旁核区域的Fra-like和AT1-R表达明显减少(P<0.05)。结论心力衰竭时室旁核区域的AT1-R被明显激活伴有交感神经放电增加,促进心力衰竭的发展。Objective To investigate whether angiotensin type 1 receptor （ATI-R） is activated in the PVN, and whether the activated AT1-R contributes to renal sympathetic nerve activity （RSNA） in heart failure （HF） rats Methods Adult male Sprague-Dawley rats were implanted with PVN cannulae for chronic infusion of the different drugs. A week later, rats are subjected to left coronary artery ligation to induce heart failure and SHAM rats did not undergo coronary ligation. Subsequently, an Alzet osmotic minipump was attached to the PVN cannula for chronic infusion of the AT1-R antagonist valsartan （0.05 μg/h） or artificial cerebrospinal fluid （aCSF, 0.11 μ/h） for 4 weeks. At the end of 4 weeks, left ventricular function was measured by the hemodynamic parameters. Some rats were anaesthetized for terminal electrophysiological studies; Lung/ body weight ratio （L/BW） and right ventricle/ body weight ratio （RVW/BW） was calculated; Plasma NE and Ang Ⅱ content were measured; Fra-like and AT1-R protein levels of the PVN was measured with Western blot technique. Results Compared with SHAM rats, HF rats had a decrease in left ventricular function, a significant increase in RSNA, the expression of Fra-like（markers of activated neurons） and ATI -R in the PVN, plasma angiotensin Ⅱ （Ang Ⅱ ） and norepinephrine （NE） levels （P〈0.05）. In contrast, PVN treated with valsartan attenuated Fra-like and AT1-R expression in the PVN compared with aCSF-treated HF rats, and recovered cardiac function partly. The treatment also decreased RVW/BW and L/BW and reduced plasma levels of NE and Ang Ⅱ （P〈 0.05）. Conclusion These findings confirm that activated AT1-R in the PVN contribute to the increased sympathetic nerve activity and the pathophysiology of congestive heart failure.

关 键 词：心力衰竭 充血性 室旁核 血管紧张素1型受体 肾交感神经放电 

分 类 号：R541.6[医药卫生—心血管疾病]