本文選題：心肌梗塞 + 骨髓��； 參考：《中國(guó)組織工程研究》2017年09期

【摘要】：背景:最近發(fā)現(xiàn),miR-378能調(diào)節(jié)骨髓間充質(zhì)干細(xì)胞的抗缺氧能力,減輕其在缺氧環(huán)境下的凋亡。目的:觀察miR-378過表達(dá)骨髓間充質(zhì)干細(xì)胞在大鼠心肌梗死模型中的治療作用。方法:體外培養(yǎng)至第3代的大鼠骨髓間充質(zhì)干細(xì)胞用反轉(zhuǎn)錄病毒感染建立miR-378過表達(dá)細(xì)胞系。選用成年SD大鼠,結(jié)扎前降支制作急性心肌梗死模型,隨機(jī)分為3組:對(duì)照組(n=10)、BMSC~(null)組(n=16)、BMSC~(miR-378)組(n=16)。對(duì)照組僅注射50μL生理鹽水,后2組梗死局部注射50μL生理鹽水中含1×10~7個(gè)空病毒轉(zhuǎn)染和miR-378模擬物轉(zhuǎn)染的骨髓間充質(zhì)干細(xì)胞。移植24 h后,利用TUNEL染色測(cè)定移植骨髓間充質(zhì)干細(xì)胞的凋亡率,Western blotting檢測(cè)移植區(qū)域內(nèi)血管內(nèi)皮生長(zhǎng)因子、轉(zhuǎn)化生長(zhǎng)因子β1蛋白表達(dá)。移植4周后,利用心臟超聲評(píng)價(jià)心功能,取局部心肌組織行組織學(xué)及分子生物學(xué)分析。結(jié)果與結(jié)論:(1)移植24 h后,BMSC~(miR-378)組中凋亡細(xì)胞明顯少于BMSC~(null)組(n=6,P0.001),血管內(nèi)皮生長(zhǎng)因子、轉(zhuǎn)化生長(zhǎng)因子β1表達(dá)水平明顯高于BMSC~(null)組(n=6,P0.001);(2)移植4周后,BMSC~(miR-378)組中存活和分化為心肌細(xì)胞的骨髓間充質(zhì)干細(xì)胞數(shù)量明顯多于BMSC~(null)組(n=10,P0.001)。與其他2組相比,BMSC~(miR-378)組中新生血管數(shù)量明顯增多(P0.001);心肌梗死面積明顯減小(P0.001);左室射血分?jǐn)?shù)明顯增加(P0.05);左室舒張末容積明顯縮小(P0.05)。BMSCnull組中上述參數(shù)明顯優(yōu)于對(duì)照組(P0.05);(3)結(jié)果表明,miR-378過表達(dá)可提高移植骨髓間充質(zhì)干細(xì)胞的抗缺氧能力,繼而促進(jìn)心肌修復(fù)。
[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.
【作者單位】： 中國(guó)醫(yī)科大學(xué)附屬第一醫(yī)院循環(huán)內(nèi)科;撫順礦務(wù)局總醫(yī)院循環(huán)內(nèi)科;
【基金】：遼寧省科學(xué)技術(shù)計(jì)劃項(xiàng)目(2012225084) 沈陽市科學(xué)技術(shù)項(xiàng)目(F12-193-9-03、F16-206-9-08) 遼寧省教育廳科學(xué)研究一般項(xiàng)目(L2013316)~~
【分類號(hào)】：R542.22

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