自体骨骼肌卫星细胞心肌移植对心肌梗死大鼠心肌纤维化的影响  

Effects on myocardial fibroatrophy in rats with myocardial infarction by auto-skeletal muscle satellite cell implanted into ischemic myocardium

作　　者：王红勇[1] 何作云[2] 于长青[1] 向德兵[1] 胡厚祥[1] 王毅[1] 杨成明[1] 王旭开[1] 傅春江[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心内科,重庆400042 [2]第三军医大学新桥医院心内科,重庆400037

出　　处：《重庆医学》2008年第6期566-568,571,共4页Chongqing medicine

摘　　要：目的了解自体骨骼肌卫星细胞(satellite cell,SC)心肌移植对心肌梗死(myocardial infarction,MI)大鼠心肌纤维化的影响及可能机制。方法45只Wistar大鼠随机分为假手术组(n=15)、对照组(n=15)及移植组(n=15),对照组及移植组大鼠经结扎冠状动脉前降支建立MI模型;假手术组除不结扎左前降支外,其余操作同对照组和移植组。将体外培养2周的大鼠自体SC以注射的方式移植到移植组大鼠梗死区周围,4周后测定各组大鼠缺血心肌VEGFmRNA的表达、VEGF蛋白质的表达、缺血心肌毛细血管密度的变化及缺血心肌的纤维化程度,同时观察移植细胞在梗死区的生长、增殖情况并探讨它们相互的关系。结果SC在梗死区中可增殖分化为横纹肌纤维;SC移植4周后,与假手术组比较,对照组大鼠缺血心肌中毛细血管密度明显增高,差异有统计学意义(P<0.05),而移植组大鼠缺血心肌中毛细血管密度及VEGFmRNA、VEGF蛋白质的表达较之假手术组、对照组亦明显升高,差异有统计学意义(P<0.05或0.01或0.001)。移植组心肌梗死区域的纤维化被有效抑制,而对照组则呈现出明显的纤维化特征。结论SC在心肌梗死区中可增殖分化为具有弹性和收缩功能的横纹肌样细胞,并通过自分泌和旁分泌的形式分泌VEGF促使缺血心肌毛细血管增生,从而有效地抑制了缺血心肌的纤维化进程。Objective To investigate the effects on myocardial fibroatrophy in rats with myocardial infarction by auto-skeletal muscle satellite cell implanted into ischemic myocardium and their mechanisms. Methods Approximately 107-109 SCs were cultivated in vitro from Wistar rats whose left anterior descending（LAD） artery had been ligated to create a myocardial infarction（MI）. Two weeks after MI , autologous SCs, serum-free culture medium and sodium chloride injection were injected into ischemic myocardium of implantation（n= 15） ,control（n= 15） and myocardium around LAD of sham operation（SO, n = 15） animals, respectively. Four weeks after injection, capillary density in the ischemic myocardium were demonstrated by immunohistochemical method. At the same rime,the expression of VEGF protein in the ischemic myocardium was demonstrated by immunohistochemical method,and the expression of VEGFmRNA in the ischemic myocardium was detected by reverse transcription polymerase chain reaction（RT-PCR）. The differentiated myofibers from SCs and myocardial fibroatrophy in the infarcted site were observed by pathologic examination and immunohistochemical method. Results Four weeks after injection,the SCs had progressively differentiated into striated muscle fibers in the myocardial infarction site, and immunohistochemical analysis comfirmed their skeletal muscle origin. Compared with the SO group, capillary density was markedly increased in the control group and implantation group（P〈0.05,0. 001）. Capillary density in the implantation group was higher than that in the SO and in the control group（P〈0. 05 or 0. 01 or 0. 001）. Compared with the SO and control group,the expression of VEGFmRNA and VEGF protein in the isehemie myocardium were markedly increased in the implantation group（P〈0.01 or 0. 001）. At the same time, myocardial fibroatrophy in the implanted group was effectively inhibited compared with that in the control group. Conclusion The SCs,after being implanted into the myocardial infarctio

关 键 词：骨骼肌卫星细胞 心肌梗死 移植 血管内皮生长因子 毛细血管 纤维化 

分 类 号：R542.22[医药卫生—心血管疾病]