摘要
目的:探究慢性心衰大鼠下丘脑室旁核(PVN)内花生四烯酰乙醇胺(AEA)对心脏功能和交感神经活动的影响。方法:采用冠状动脉结扎法构建大鼠心衰模型,超声心动图检测心功能;PVN内连续4周分别灌注AEA、钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)选择性抑制剂KN-93、瞬时受体电位香草酸亚型1(TRPV1)通道特异性阻断剂辣椒平(CPZ)、Ca^(2+)螯合剂BAPTA-AM和小电导钙激活钾通道(SK通道)阻断剂apamin后,检测交感驱动及心功能指标;同时采用不同浓度AEA孵育NG108细胞,荧光测定法检测细胞内钙离子浓度([Ca^(2+)]_i);Western blot检测CaMKII、SK_2及磷酸化TRPV1蛋白水平。结果:与假手术组相比,心衰组左心室舒张末期压(LVEDP)明显升高,左室压力最大上升、下降速率(±dp/dt_(max))和射血分数(EF)明显下降;PVN内AEA含量、[Ca^(2+)]_i及CaMKII、SK_2和磷酸化TRPV1蛋白水平均显著降低;与溶剂组相比,心衰组PVN内灌注AEA可显著降低心衰大鼠死亡率和交感驱动指标,并改善心功能;然而,PVN内分别灌注KN-93、CPZ、BAPTA-AM和apamin均显著增强交感驱动指标并恶化心功能;AEA可剂量依赖性增加NG108细胞内[Ca^(2+)]_i及CaMKII、SK_2和磷酸化TRPV1蛋白水平。结论:室旁核内CaMKII/TRPV1/Ca^(2+)/SK_2信号通路可能参与了AEA对心衰大鼠心脏功能和交感神经活动的影响。
AIM:To determine the roles of the arachidonylethanolamide(AEA)in the paraventricular nucleus(PVN)in cardiac function and sympathetic activity in the rats with chronic heart failure(CHF).METHODS:Chronic heart failure was induced by left coronary ligation in Wistar rats and was confirmed using echocardiography.The rats with CHF and the sham-operated controls(sham group)were treated for 4 weeks with a continuous PVN infusion of AEA,cal-cium-calmodulin-dependent protein kinase II(CaMKII)selective inhibitor KN-93,transient receptor potential vanilloid type 1(TRPV1)channel blocker capsazepine(CPZ),intracellular calcium chelator BAPTA-AM,small-conductance calcium-activated potassium channel(SK channel)blocker apamin and artificial cerebrospinal fluid(vehicle).Sympathetic drive indexes and cardiac function were detected.NG108 cells were incubated with AEA,and then the intracellular cal-cium concentration was measured by fluorometry.The protein expression levels of CaMKII,SK 2 and phosphorylated TRPV1 were determined by Western blot.RESULTS:Compared with sham group,the left ventricular end-diastolic pressure(LVEDP)increased significantly,while peak rate of rise/decline of left ventricular pressure(±d p/d t max)and ejection fraction(EF)decreased significantly in the CHF group.The concentrations of AEA and intracellular calcium,and the protein levels of CaMKII,SK 2 and phosphorylated TRPV1 in PVN were significantly lower in CHF rats.Compared with the vehicle group,the mortality and sympathetic drive were decreased significantly and cardiac function was improved after treatment with AEA in CHF group.However,PVN perfusion of KN-93,CPZ,BAPTA-AM or apamin contributed to the sympathetic drive and deteriorated the cardiac function.AEA dose-dependently increased intracellular calcium ion concentration,and the protein levels of CaMKII,SK 2 and phosphorylated TRPV1 in NG108 cells.CONCLUSION:AEA in the PVN may be involved in the improvement of cardiac function and sympathetic overdrive via CaMKII/TRPV1/Ca 2+/SK 2 pathway in rats wi
作者
王仁俊
周琴
未晓巍
李华
赵永斌
齐云峰
栾剑
周晓馥
WANG Ren-jun;ZHOU Qin;WEI Xiao-wei;LI Hua;ZHAO Yong-bin;QI Yun-feng;LUAN Jian;ZHOU Xiao-fu(Department of Biotechnology,School of Life Science,Jilin Normal University,Siping 136000,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第9期1537-1545,共9页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81202527)
吉林省科技发展计划项目(No.20130522002JH)
关键词
慢性心力衰竭
室旁核
花生四烯酰乙醇胺
心脏功能
交感神经系统
Chronic heart failure
Paraventricular nucleus
Arachidonylethanolamide
Cardiac function
Sympathetic nervous system
