ErbB信号与蛋白激酶B在快速起搏所致猴心衰心肌细胞损伤中的作用  

Effects of ErbB signal and protein kinase B on monkey cardiocyte apoptosis induced by rapid pacing

作　　者：李江[1] 陈又南[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,四川成都610041 [2]四川大学华西医院移植工程与移植免疫实验室,四川成都610041 [3]四川大学华西医院国家(成都)中药安全性评价中心,四川成都610041

出　　处：《药学学报》2007年第5期470-474,共5页Acta Pharmaceutica Sinica

基　　金：高等学校博士学科点专项科研基金资助课题(20050610070).

摘　　要：为了研究ErbB受体与蛋白激酶B在心力衰竭发生机制中的作用,建立快速起搏诱导恒河猴心力衰竭模型。采用颈总动脉插管技术,测定左心室最大压力上升速度(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;采用电化学发光免疫测定法观察脑钠肽(BNP)含量;采用RT-PCR方法测定ErbB2、蛋白激酶B(PKB)、Bcl-xl mRNA表达水平;采用Western blotting检测蛋白激酶B活性(phospho-PKB,即磷酸化蛋白激酶B蛋白水平)及凋亡相关基因Bcl-xl的蛋白水平。快速起搏诱导心力衰竭模型恒河猴心肌收缩能力显著下降,心衰标志物脑钠肽水平明显上升(P<0.05)。与对照组比较ErbB2,PKB及Bcl-xl mRNA表达水平明显下降(P<0.05),同时心肌组织蛋白激酶B活性显著下降,Bcl-xl蛋白水平也明显下降(P<0.05)。快速起搏所致猴心衰心肌细胞损伤的机制可能与ErbB2、下游蛋白激酶B、凋亡抑制基因Bcl-xl表达水平下降及蛋白激酶B活性下降有关。This study is to investigate the roles of neuregulin receptor ErbB2 and protein kinase B （PKB） in pacing-induced heart failure of rhesus monkey. Rapid pacing was used to induce heart failure in rhesus monkey. Aorta intubatton was used to perform hemodynamic measurements, 17 days after pacing. N-Terminal pro-brain natriuretic peptide （BNP） , one of the most important molecular marker of heart failure, was also measured by the method of electrochemical luminescence immunoassay. The mRNA expressions of ErbB2 , PKB and Bcl-xl were detected in the left ventricular free walls by RT-PCR method. The expressions of phospho-PKB and Bcl-xl on protein level were also detected by Western blotting. The contractibility of cardiac muscle decreased significantly, which consisted with the increase of BNP. Compared with control group, the mRNA expressions of ErbB2, PKB and Bcl-xl were depressed, and similar results were also found in the protein expression analysis of phospho-PKB and Bcl-xl. The expressions of ErbB2, PKB and Bcl-xl were down-regulated during heart failure in rhesus monkey which suggested the important roles of ErbB2 receptor and PKB in the mechanism of heart failure.

关 键 词：心力衰竭 细胞凋亡 ErbB2受体 蛋白激酶B 

分 类 号：R963[医药卫生—微生物与生化药学]