神经胶质细胞生长因子对快速起搏所致猴心衰的保护作用及机制研究  

Effects of Neregulin on Rhesus Monkey Heart Failure Induced by Rapid Pacing

作　　者：刘小波[1] 李江[1] 肖溢[1] 庞凌烟[1] 蒋星[1] 王莉[1] 

机构地区：[1]四川大学华西医院国家成都中药安全性评价中心,成都610041

出　　处：《四川大学学报（医学版）》2009年第1期93-96,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的研究重组人神经胶质细胞生长因子(NRG)对快速起博所致猴心衰心肌收缩力的影响及给予重组人NRG后心肌细胞内葡萄糖转运蛋白1(Glut1)mRNA表达水平的变化。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NRG治疗组,每组8只。治疗组240次/min起搏7d后,起搏状态下连续10d,每天1次静脉注射重组人NRG3μg/kg,心力衰竭组给予同体积生理盐水。连续给药10d结束后,测定左心室的最大压力上升速度(LVdp/dtmax)、左心室舒张末期压(LVEDP)、左心室收缩末期压(LVSP)等血流动力学指标。提取左室心肌组织mRNA,采用RT-PCR的方法分析PKB、Glut1mRNA的表达水平。Western Blotting测定心室肌磷酸化PKB蛋白含量。结果心力衰竭组LVdp/dtmax、LVSP低于假手术组(P<0.05),LVEDP高于假手术组(P<0.05);NRG治疗组LVdp/dtmax高于心力衰竭组(P<0.05),LVSP有上升的趋势(上升了11%),LVEDP有下降的趋势(下降了39%)。心力衰竭组PKB、Glut1mRNA表达水平均低于假手术组(P<0.05);治疗组PKB、Glut1mR-NA表达水平高于心力衰竭组(P<0.05)。治疗组磷酸化PKB蛋白水平比心力衰竭组上升了177%(P<0.05)。结论重组人NRG可能通过向上调节PKB、Glut1mRNA表达水平,改善缺血心肌能量供应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 investigate the effects of Recombined Human Neuregulin （NRG） on the expression of Glucose transporter （Glut1） in myocardium tissue of Rhesus Monkeys with Pacing-induced Heart Failure and the heart function. Methods Twenty four rhesus monkeys were randomly divided into three groups （shame operated group, heart failure group and NRG treated group）, each with 8 monkeys. Heart failures were induced by rapid pacing （240 heart beats/min）. Daily intravenous injection of recombined human NRG [3 μg/（kg · d）] and normal saline were given to the monkeys for 10 clays for the NRG treated group and heart failure group respectively. Hemodynamic measurements including ＋dp/dtmax and left ventricular systolic, end-diastolic blood pressures （LVSP and LV- EDP） were conducted. The RT-PCR was applied to detect the expression level of PKB, Glut1 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 NRG treated group had higher levels of ＋dp/dtmax than those in the heart failure group （P〈0.05）. Lower expression of PKB, Glut1 mRNA in the heart failure group was observed compared with the shame operated group （P〈0.05） while the NRG treated group had a higher expression level of PKB,Glut1 mRNA by compared with the heart failure group （P〈 0.05）. Conclusion Recombined human NRG can relieve heart failure syndroms through up-regulating the expression of PKB,Glut1 mRNA and improving energy supply of the ischemic cardiac muscle.

关 键 词：神经胶质细胞生长因子 心力衰竭 葡萄糖转运蛋白 基因表达血流动力学 

分 类 号：R541.6[医药卫生—心血管疾病]