首页|室旁核lncRNA HFAR介导SK2在慢性心力衰竭中的调控机制探究

室旁核lncRNA HFAR介导SK2在慢性心力衰竭中的调控机制探究

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交感神经系统活动过度增强是慢性心力衰竭(chronic heart failure,CHF)的重要病理特征之一,是加速CHF病情恶化的主要因素.为阐明室旁核(paraventricular nucleus,PVN)中的长链非编码RNA(long non-codin-gRNA,lncRNA)心力衰竭相关调节剂(Heart failure associated regulator,HFAR),调控2型小电导钙激活钾通道蛋白(small-conductance Ca2+-activated K+channel 2,SK2)参与CHF发生发展的内在机制.采用结扎大鼠冠状动脉左前降支建立CHF模型,通过qRT-PCR方法在CHF大鼠下丘脑PVN组织和血管紧张素Ⅱ(angiotension Ⅱ,ANGⅡ)孵育的原代培养新生乳鼠下丘脑神经元细胞中,筛选出表达下调显著的lncRNA HFAR(p<0.001);进一步利用心脏彩超检测、交感神经放电记录方法、免疫荧光和 Western blot技术,发现过表达PVN内lncRNA HFAR可显著改善CHF大鼠心功能、抑制交感神经兴奋亢进和显著上调SK2的表达(p<0.05).结果表明:PVN中下调显著的lncRNA HFAR通过靶向SK2参与CHF大鼠交感神经兴奋的调节,这将为CHF治疗提供一种新策略.
Exploration of the Regulatory Mechanism of Paraventricular Nucleus lncRNA HFAR Mediating SK2 in Chronic Heart Failure
Sympathetic nerve overactivity is one of the important pathological characters in chronic heart failure(CHF),and is the key factor accelerating the deterioration of CHF.The aim of this study was to e-lucidate the intrinsic mechanism of long chain non-coding RNA(lncRNA)heart failure-related regulator in paraventricular nuclei(PVN)regulate type 2 small conductance calcium-activated potassium channel(SK2)protein involved in the occurrence and development of CHF.The CHF rat model was established by ligation of the left anterior descending branch of the coronary artery.Down-regulated lncRNA HFAR was screened from the hypothalamic PVN tissue of CHF rats and the hypothalamic neurons incubated with an-giotensin Ⅱ(ANGⅡ)by qRT-PCR method(p<0.001).Furthermore,investigation with cardiac ultra-sound detection,sympathetic nerve discharge recording methods,immunofluorescence and western blot technology indicated that overexpression of lncRNA HFAR in PVN can significantly improve the cardiac function,inhibit sympathetic nerve overactivity and upregulate SK2 expression in rats with CHF(p<0.05).The results show that down-regulated lncRNA HFAR in PVN was involved in the regulation of sympathetic nerve overactivity in CHF rats by targeting SK2,which provides a new strategy for the treat-ment of CHF.

paraventricular nucleusheart failure associated regulatortype 2 small conductance calcium activates potassium channelsympathetic nerve activitychronic heart failure

杨玉莹、刘京、刘海峰、孙巍、赵静岩、张敏、王仁俊、杨一

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吉林师范大学生命科学学院,吉林四平 136000

四平市中心人民医院,吉林四平 136000

室旁核 心力衰竭相关调节剂 2型小电导钙激活钾通道 交感神经活动 慢性心力衰竭

2025

西南大学学报(自然科学版)
西南大学学报编辑部

西南大学学报(自然科学版)

北大核心
影响因子:0.825
ISSN:1673-9868
年,卷(期):2025.47(1)