重组人Neureguline对快速起搏所致猴心衰心肌收缩能力的影响及其机制研究  

Effects of Recombined Human Neuregulin on the Contractibility of Cardiac Muscles of Rhesus Monkeys with Pacing-induced Heart Failure

作　　者：李江[1] 顾兴华[2] 段嘉川[3] 曾理[3] 李尤[3] 王莉[3] 

机构地区：[1]四川大学华西药学院,成都610041 [2]复旦大学附属中山医院心血管病研究所 [3]四川大学华西医院国家成都中药安全性评价中心

出　　处：《四川大学学报（医学版）》2007年第1期105-108,共4页Journal of Sichuan University(Medical Sciences)

基　　金：教育部高等学校搏士学科点科研基金(20050610070)资助

摘　　要：目的研究重组人N euregu line对快速起搏所致心力衰竭恒河猴心肌收缩能力的影响,并探讨其可能的机理。方法成年雄性恒河猴24只,随机分为假手术组、心力衰竭组及N euregu line治疗组,每组8只。治疗组240次/m in起搏7 d后,起搏状态下连续10 d,每天1次静脉注射重组人N euregu line 3μg/kg,心力衰竭组给予同体积生理盐水。连续给药10 d结束后,测定左心室的最大压力上升速度(LV dp/dtm ax)、左心室舒张末期压(LVEDP)、左心室收缩末期压(LV SP)等血流动力学指标。提取左室心肌组织mRNA,采用实时荧光定量PCR的方法分析肌球蛋白重链(-αMyH C)的表达水平。结果心力衰竭组LV dp/dtm ax、LV SP低于假手术组(P<0.05),LVEDP高于假手术组(P<0.05);N euregu line治疗组LV dp/dtm ax高于心力衰竭组(P<0.05),LV SP有上升的趋势(上升了11%),LVEDP有下降的趋势(下降了16%)。心力衰竭组-αMyH C表达水平低于假手术组(P<0.05);治疗组-αMyH C表达水平高于心力衰竭组(P<0.05)。结论重组人N euregu lin可能通过向上调节-αMyH C表达水平这一机制来增强心肌收缩力,从而达到治疗心衰的目的。Objective To evaluate the effects of recombined human Neuregulin on the contractibility of cardiac muscles of Rhesus Monkeys with pacing-induced heart failure and to reveal the possible mechanisms involved. Methods Twenty four rhesus monkeys were randomly divided into three groups （shame operated group, heart failure group and Neuregulin treated group）, each with 8 monkeys. Heart failures were induced by rapid pacing （240 heartbeats/min）. Daily intravenous injection of recombined human Neuregulin [3μg/（kg·d）]and medical salt fluid were given to the monkeys for 10 days for the Neuregulin treated group and heart failure group respectively. Hemodynamic measurements such as peak positive rate of change in left ventricular blood pressure （＋dP/dtmax） and left ventricular systolic, and end-diastolic blood pressures （LVSP and LVEDP） were compared between groups. The real-time quantitative RT-PCR was undertaken to detect the expression of myosin heavy chain mRNA in the left ventricular cardiac muscle. Results The monkeys in the heart failure group had lower levels of ＋dP/dtmax and LVSP and higher levels of LVEDP than those in the shame operated group （P〈0.05）. The monkeys in the Neuregulin treated group had higher levels of ＋dP/dtmax than those in the heart failure group （P〈0. 05）. Lower expression of α-myosin heavy chain mRNA in the heart failure group was found compared with the shame operated group and Neuregulin treated group （P〈0.05）. Conclusion Recombined human Neuregulin can enhance the contractibility of cardiac muscles and relieve heart failure syndrome through reversing the falling of α-myosin heavy chain induced by rapid ventricular pacing.

关 键 词：NEUREGULIN 心力衰竭 肌球蛋白重链 基因表达 血流动力学 

分 类 号：R96[医药卫生—药理学]