Wnt1增强骨骼肌成肌细胞治疗心肌梗死的功能  

Wnt1 enhances skeletal myoblast function to treat myocardial infarction

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作  者:杜文娟[1] 杨艳波 张希玲[1] 许友升[1] 王世鹏[1] 

机构地区:[1]哈尔滨医科大学附属第二医院心血管内科,黑龙江哈尔滨150081 [2]哈尔滨市第二医院心内科,黑龙江哈尔滨150001

出  处:《哈尔滨医科大学学报》2016年第2期103-108,共6页Journal of Harbin Medical University

基  金:黑龙江省教育厅科学技术研究项目(12511296)

摘  要:目的探讨Wnt1基因对骨骼肌成肌细胞(skeletal myoblasts,SkMs)治疗心肌梗死(myocardial infarction,MI)功能的影响及其机制。方法分离培养SkMs,构建p-EGFP-C3-Wnt1真核表达载体并转染SkMs。采用随机数字表法将40只大鼠分为假手术组、MI组、p-EGFP-C3转染SkMs心肌移植组、pEGFP-C3-Wnt1转染SkMs心肌移植组,每组10只。MI组大鼠结扎其左冠状动脉前降支建立MI模型;细胞移植组大鼠,建立MI模型后立即于梗死边缘区分4点进行细胞移植。术后4周,心脏超声检测各组鼠心功能;应用激光共聚焦显微镜检测移植细胞存活情况和缝隙连接蛋白43(connexin43,Cx43)表达;应用免疫组化检测Sca-1+细胞表达。结果 p-EGFP-C3-Wnt1转染的SkMs心肌移植组移植细胞存活数量、Cx43表达、心脏功能均明显高于p-EGFP-C3转染的SkMs心肌移植组(P<0.01),并在p-EGFPC3-Wnt1转染的SkMs心肌移植大鼠心脏中发现了更多的Sca-1+心肌干细胞(cardiac stem cells,CSCs)。结论过表达Wnt1的SkMs通过促进移植细胞存活,增加心肌Cx43表达、促进Sca-1+CSCs归巢,改善MI大鼠的心脏功能。Objective To investigate the effect and mechanism of Wnt1 gene on skeletal myoblasts( SkMs) for cardiac transplantation to treat myocardial infarction( myocardial infarction,MI). Methods SkMs was isolated and cultured,and p-EGFP-C3-Wnt1 eukaryotic expression vector was constructed and transfected into SkMs. Forty rats were randomly divided into sham group,MI group,p-EGFP-C3 transfected SkMs cardiac transplantation group,p-EGFP-C3-Wnt1 transfected SkMs cardiac transplant group,ten rats in each group. Rats were ligated the left anterior descending coronary artery to establish MI model; After establishing MI in rats,SkMs were injected immediately at four different points in infarct border. Four weeks after operation,heart function was detected by echocardiography; The survival of the transplanted cells connexin 43( connexin43,Cx43) expression were detected by laser scanning confocal microscopy. Sca-1+cardiac stem cells( CSCs) were detected by immunohistochemistry. Results The number of cell survival,Cx43 expression in myocardial tissue,cardiac function were significantly higher in p-EGFP-C3-Wnt1 transfected SkMs cardiac transplantation group than the p-EGFP-C3 transfected SkMs cardiac transplantation group( P 〈 0. 01),and more Sca-1+CSCs were found in rat hearts of p-EGFP-C3-Wnt1 transfected SkMs cardiac transplantation group.Conclusion Wnt1 overexpressing SkMs improve heart function in rats with MI by promoting survival of transplanted cells,increasing Cx43 expression of myocardium,and promoting Sca-1+CSCs homing.

关 键 词:骨骼肌成肌细胞 心肌梗死 WNT1 细胞移植 Sca-1+心肌干细胞 

分 类 号:R542.22[医药卫生—心血管疾病]

 

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