Cardiac autonomic nerve fiber regeneration in chronic heart failure Do Akt gene-transduced mesenchymal stem cells promote repair?

作     者：Hongliang Kong Zhanquan Li Shumei Zhao Li Zhu Yingjun Zhao Weiwei Zhang GuipingXu Wenjun Hao Huijun Li Guoxian Qi 

作者机构：Department of Cardiology the First Affiliated Hospital of China Medical University Shenyang 110001 Liaoning Province China Department of Cardiology the People's Hospital of Liaoning Province Shenyang 110016 Liaoning Province China Shenyang Normal University Shenyang 110034 Liaoning Province China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2010年第5卷第1期

页      面：28-34页

核心收录：

学科分类：10[医学] 

基　　金：Scientific Research Program of Higher Education Institute in Liaoning Province  No. 2008S248 

主　　题：mesenchymal stem cells Akt gene transfection chronic heart failure neural regeneration autonomic nerve system 

摘      要：BACKGROUND： Transplantation of Akt-over-expressing mesenchymal stem ceils （Akt-MSCs） has been shown to repair infarcted myocardium and improve cardiac function. However, little is known about the therapeutic effects of Akt-MSCs on cardiac autonomic neuropathy in chronic heart failure （CHF）. OBJECTIVE： The present study used adriamycin-induced CHF rat models to observe the effect of Akt-MSCs on cardiac autonomic nervous regeneration and the factors mediating this effect. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Central Laboratory of Basic Medical College, China Medical University, between September 2008 and April 2009. MATERIALS： Rabbit anti-choline acetyltransferase （CHAT）, growth associated protein-43 （GAP-43） synaptophysin （SYN） polyclonal antibodies and the secondary antibody （goat anti-rabbit IgG） were purchased from Boster, China. Cat-A-Kit assay system was provided by Amersham, USA. METHODS： （1） Adult rat MSCs were isolated and cultured for the preparation of Akt-MSCs. （2） Forty male Wistar rats were intramyocardially administered adriamycin at 2 mg/kg over 3 days for a total of five times and once a week for additional five times thereafter to establish CHF models. At 2 weeks after final adriamycin treatment, 34 successful CHF rat models were randomized to three groups： Akt-MSCs （n = 11）, simple MSCs （s-MSCs, n =11）, and control （n = 12）. Each group was intravenously administered Akt-MSCs （2x106 cells in 100 IJL PBS）, s-MSCs （2×10^6 cells in 100 μL PBS） or equal volume of phosphate buffered saline, once a day for a total of three times. MAIN OUTCOME MEASURES： At 4 weeks after final adriamycin treatment, myocardial norepinephrine （NE） content was detected using a Cat-A-Kit assay system. Myocardial CHAT, SYN and GAP-43 were performed by immunohistochemistry and Western blot analysis. Prior to, 2 and 4 weeks after adriamycin treatment, echocardiographic examination was performed and left ventricular ejection fract