法舒地尔联合骨髓间充质干细胞移植治疗大鼠急性心肌梗死:有协同治疗作用吗?  

Fasudil combined with bone marrow mesenchymal stem cell transplantation for acute myocardial infarction in rats:Do synergistic therapeutic effect exist?

作　　者：王丽君 范广明 

机构地区：[1]凌源市第一人民医院,辽宁省凌源市122500 [2]朝阳市中心医院,辽宁省朝阳市122000

出　　处：《中国组织工程研究与临床康复》2010年第19期3490-3494,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:RhoA激酶抑制剂法舒地尔能有效抑制心肌梗死后的心肌肥大。目的:观察法舒地尔联合骨髓间充质干细胞移植对急性心肌梗死模型鼠心功能的影响,探讨两者是否具有协同治疗作用。方法:体外培养扩增SD大鼠骨髓间充质干细胞,另选取42只雌性SD大鼠结扎前降支,建立急性心肌梗死模型,随机分成3组。干细胞组,干细胞+法舒地尔组梗死心肌中移植骨髓间充质干细胞,干细胞+法舒地尔组同时给予法舒地尔治疗,梗死组不干预。4周后,以二维超声心动图分析心功能变化,SRY-PCR检测大鼠Y染色体上特有的基因SRY,Western-Blot检测RhoA蛋白表达,并进行病理观察。结果与结论:与梗死组比较,干细胞组和联合组左室舒张末内径及左室收缩末内径均显著减小(P<0.01),射血分数均显著升高(P<0.01),其中干细胞+法舒地尔组变化幅度优于细胞移植组(P<0.05)。干细胞组和联合组基因有SRY表达,梗死组未检测到基因SRY。干细胞+法舒地尔组RhoA蛋白表达水平较梗死组、干细胞组显著降低(P<0.05)。病理观察干细胞组和联合组心肌修复优于梗死组,干细胞+法舒地尔组较干细胞组明显。结果表明单纯骨髓间充质干细胞移植以及法舒地尔联合骨髓间充质干细胞移植均可改善心肌梗死大鼠心功能,减少心室扩张程度,两者联合情况下效果最佳,对心肌梗死具有协同治疗作用。BACKGROUND：RhoA kinase inhibitor Fasudil can effectively suppress cardiac hypertrophy following myocardial infarction.OBJECTIVE：To observe the effects of Fasudil combined with bone marrow mesenchymal stem cell（BMSC） transplantation on cardiac function in rat models of acute myocardial infarction（AMI）,and to investigate the synergetic therapeutic effects of Fasudil and BMSC transplantation.METHODS：BMSCs were incubated and amplified in Sprague Dawley rats in vitro.An additional 42 adult female Sprague Dawley rats were selected to ligate the anterior descending branch to establish models of AMI.These rats were randomly assigned to three groups.BMSCs were injected into rats in the BMSC transplantation group.BMSC transplantation and Fasudil treatment were performed in BMSC transplantation ＋ Fasudil group.Rats in the myocardial infarction group were left intact.Four weeks post-transplantation,two-dimensional echocardiography was used to detect cardiac function.SRY-PCR was used to detect the SRY gene which is a specific marker of Y chromosome.Western blot assay was utilized to detect RhoA protein expression,and the pathology was checked.RESULTS AND CONCLUSION：Compared with myocardial infarction group,left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly decreased in the BMSC transplantation group and BMSC transplantation ＋ Fasudil group（P 0.01）,but ejection fraction was significantly increased（P 0.01）.The changes were better in BMSC transplantation ＋ Fasudil group compared with BMSC transplantation group（P 0.05）.The SRY expression was determined in BMSC transplantation group and BMSC transplantation ＋ Fasudil group,but no SRY gene was detected in myocardial infarction group.The protein expression level of RhoA significantly decreased in BMSC transplantation ＋ Fasudil group than in myocardial infarction group and BMSC transplantation group（P 0.05）.Myocardial repair was better in the BMSC transplantation group and BMSC transplantatio

关 键 词：法舒地尔 心肌梗死 骨髓间充质干细胞 移植 SRY 

分 类 号：R394.2[医药卫生—医学遗传学]