过表达miR-378骨髓间充质干细胞移植治疗心肌梗死

发布时间：2018-05-19 19:25

本文选题：心肌梗塞 + 骨髓　；参考：《中国组织工程研究》2017年09期

【摘要】：背景:最近发现,miR-378能调节骨髓间充质干细胞的抗缺氧能力,减轻其在缺氧环境下的凋亡。目的:观察miR-378过表达骨髓间充质干细胞在大鼠心肌梗死模型中的治疗作用。方法:体外培养至第3代的大鼠骨髓间充质干细胞用反转录病毒感染建立miR-378过表达细胞系。选用成年SD大鼠,结扎前降支制作急性心肌梗死模型,随机分为3组:对照组(n=10)、BMSC~(null)组(n=16)、BMSC~(miR-378)组(n=16)。对照组仅注射50μL生理盐水,后2组梗死局部注射50μL生理盐水中含1×10~7个空病毒转染和miR-378模拟物转染的骨髓间充质干细胞。移植24 h后,利用TUNEL染色测定移植骨髓间充质干细胞的凋亡率,Western blotting检测移植区域内血管内皮生长因子、转化生长因子β1蛋白表达。移植4周后,利用心脏超声评价心功能,取局部心肌组织行组织学及分子生物学分析。结果与结论:(1)移植24 h后,BMSC~(miR-378)组中凋亡细胞明显少于BMSC~(null)组(n=6,P0.001),血管内皮生长因子、转化生长因子β1表达水平明显高于BMSC~(null)组(n=6,P0.001);(2)移植4周后,BMSC~(miR-378)组中存活和分化为心肌细胞的骨髓间充质干细胞数量明显多于BMSC~(null)组(n=10,P0.001)。与其他2组相比,BMSC~(miR-378)组中新生血管数量明显增多(P0.001);心肌梗死面积明显减小(P0.001);左室射血分数明显增加(P0.05);左室舒张末容积明显缩小(P0.05)。BMSCnull组中上述参数明显优于对照组(P0.05);(3)结果表明,miR-378过表达可提高移植骨髓间充质干细胞的抗缺氧能力,继而促进心肌修复。
[Abstract]:Background: recently it has been found that miR-378 can regulate the ability of bone marrow mesenchymal stem cells to resist hypoxia and reduce their apoptosis in hypoxic environment. Aim: to observe the therapeutic effect of miR-378 overexpression bone marrow mesenchymal stem cells (BMSCs) in myocardial infarction rats. Methods: rat bone marrow mesenchymal stem cells (BMSCs) cultured to passage 3 in vitro were infected with retrovirus to establish miR-378 overexpression cell lines. Adult Sprague-Dawley rats were selected to establish acute myocardial infarction model by ligating the descending branch before ligation. They were randomly divided into three groups: control group (n = 10) and control group (n = 16). In the control group, 50 渭 L saline was injected only, and the latter two groups were injected with 50 渭 L saline containing 1 脳 10 ~ 7 empty virus transfected bone marrow mesenchymal stem cells and miR-378 mimics. 24 h after transplantation, the apoptosis rate of bone marrow mesenchymal stem cells was determined by TUNEL staining and the expression of vascular endothelial growth factor (VEGF) and transforming growth factor 尾 1 (TGF- 尾 1) were detected by Western blotting. After 4 weeks of transplantation, cardiac function was evaluated by echocardiography, and histological and molecular analysis of local myocardial tissue were performed. Results and conclusion 24 hours after transplantation, the apoptotic cells in BMSC-MIR-378 group were significantly lower than those in BMSC-null group (P 0.001), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor (VEGF). The expression level of transforming growth factor 尾 1 was significantly higher than that in BMSC / null1 group (P 0.001 / 2). 4 weeks after transplantation, the number of bone marrow mesenchymal stem cells (MSCs) in survival and differentiation into cardiomyocytes was significantly higher in the BMSCs group than in the BMSC / nulll group (n = 10, P 0.001). Compared with the other two groups, the number of neovascularization in BMSC-MIR-378) group increased significantly (P 0.001); myocardial infarction size decreased significantly (P 0.001); left ventricular ejection fraction (LVEF) increased significantly (P 0.05); left ventricular end-diastolic volume decreased significantly (P 0.05). BMSC null group was significantly superior to the control group (P 0.05). The results showed that the overexpression of miR-378 could improve the anti-hypoxia ability of bone marrow mesenchymal stem cells. In turn, it promotes myocardial repair.
【作者单位】：中国医科大学附属第一医院循环内科;抚顺矿务局总医院循环内科;
【基金】：辽宁省科学技术计划项目(2012225084) 沈阳市科学技术项目(F12-193-9-03、F16-206-9-08) 辽宁省教育厅科学研究一般项目(L2013316)~~
【分类号】：R542.22

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