Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure  

作　　者：RONG Shu-ling WANG Yong-jin WANG Xiao-lin LU Yong-xin WU Yin LIU Qi-yun MI Shao-hua XU Yu-lan 

机构地区：[1]Department of Cardiology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China [2]Department of Paediatrics, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China [3]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Tecnology, Wuhan, Hubei 430022, China [4]Department of Psychology, School of Educational Science, South China Normal University, Guangzhou, Guangdong 510631, China

出　　处：《Chinese Medical Journal》2010年第24期3626-3633,共8页中华医学杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China （No. 30470457）, Shanxi Province Natural Science Foundation （No. 2009011055-4）, and Scientific Research Foundation of High Education Institutions of Shanxi Province, China （No. 200811034）.

摘　　要：Background Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 （IGF-1） protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction （MI） and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles （BAMs） following coronary artery ligation in Sprague-Dawley rats.Methods Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 （rhIGF-1）, and green fluorescent protein （GFP）, and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups： MI-IGF group （n=6） and MI-GFP group （n=6）. The MI-IGF group received rhIGF-secreting BAM （IGF-BAMs） transplantation, and the MI-GFP group received GFP-secreting BAM （GFP-BAMs） transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups： S-IGF group （n=6）and S-GFP group （n=6）. The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.Results Primary rat myoblasts were retrovirally transduced to Background Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 （IGF-1） protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction （MI） and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles （BAMs） following coronary artery ligation in Sprague-Dawley rats.Methods Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 （rhIGF-1）, and green fluorescent protein （GFP）, and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups： MI-IGF group （n=6） and MI-GFP group （n=6）. The MI-IGF group received rhIGF-secreting BAM （IGF-BAMs） transplantation, and the MI-GFP group received GFP-secreting BAM （GFP-BAMs） transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups： S-IGF group （n=6）and S-GFP group （n=6）. The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.Results Primary rat myoblasts were retrovirally transduced to

关 键 词：heart failure muscles insulin-like growth factor-1 gene therapy 

分 类 号：R686[医药卫生—骨科学]