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[间充质干细胞移植对实验性心肌梗死大鼠心肌中与心肌素相关转录因子-A及bcl-2表达的影响]

[Impact of mesenchymal stem cells transplantation on myocardial myocardin-related transcription factor-A and bcl-2 expression in rats with experimental myocardial infarction].

作者信息

Zhong Ze, Hu Jiaqing, Sun Yong, Jiang Jun, Wu Xindong, Xiang Peng, Luo Xiuying

机构信息

Department of Cardiology, Jiande Branch, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiande 311600, China; Email:

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2015 Jun;43(6):531-6.

PMID:26420123
Abstract

OBJECTIVE

To observe the impact of mesenchymal stem cells (BMSCs) transplantation on myocardial myocardin-related transcription factor-A (MRTF-A) and bcl-2 expression in rats with experimental myocardial infarction (MI).

METHODS

Thirty rats were randomly divided into sham, MI and MI + BMSCs (1 × 10(6) injected into 4 infarct points immediately post coronary artery ligation) groups (n = 10 each).One week later, TUNEL was used to detect cardiomyocyte apoptosis, the myocardial expression of MRTF-A and bcl-2 was detected by laser scanning confocal microscope and Western blot. In vitro plasmid of MRTF-A and co-transfection with plasmids of MRTF-A and bcl-2 or mutated bcl-2 transfection into cardiomyocyte was applied to evaluate the relationship between MRTF-A and bcl-2.

RESULTS

The number of apoptotic cardiomyocytes in the sham group, MI group and MI + BMSCs group were (4.05 ± 1.56)%, (62.38 ± 8.41)% and (22.36 ± 6.17)%, respectively (P < 0.05). The protein expression of MRTF-A and bcl-2 in the MI group were significantly lower than those in sham group, while significantly upregulated in MI + BMSCs group (P < 0.05 vs. MI). In cultured neonatal rat cardiomyocyte, the expression of bcl-2 protein was significantly upregulated after transfection with MRTF-A plasmid, and bcl-2-luciferase activity significantly increased after co-transfection with plasmids of MRTF-A and bcl-2-luciferase, however, the positive regulatory effect of MRTF-A was abolished after transfection with mutated bcl-2.

CONCLUSION

Mesenchymal stem cells transplantation can effectively reduce cardiomyocyte apoptosis in this rat MI model, and upregulate the expression of MRTF-A. Consequent up-regulated bcl-2 expression might be involved in the beneficial effects of BMSCs transplantation in this model.

摘要

目的

观察间充质干细胞(BMSCs)移植对实验性心肌梗死(MI)大鼠心肌中与心肌素相关转录因子-A(MRTF-A)及bcl-2表达的影响。

方法

将30只大鼠随机分为假手术组、MI组和MI + BMSCs组(冠状动脉结扎后立即于4个梗死部位注射1×10(6)个细胞),每组10只。1周后,采用TUNEL法检测心肌细胞凋亡,通过激光扫描共聚焦显微镜及蛋白质免疫印迹法检测心肌中MRTF-A和bcl-2的表达。体外将MRTF-A质粒转染至心肌细胞,并将MRTF-A质粒与bcl-2或突变型bcl-2质粒共转染至心肌细胞,以评估MRTF-A与bcl-2之间的关系。

结果

假手术组、MI组和MI + BMSCs组心肌细胞凋亡数分别为(4.05 ± 1.56)%、(62.38 ± 8.41)%和(22.36 ± 6.17)%(P < 0.05)。MI组中MRTF-A和bcl-2的蛋白表达显著低于假手术组,而MI + BMSCs组中显著上调(与MI组相比,P < 0.05)。在培养的新生大鼠心肌细胞中,转染MRTF-A质粒后bcl-2蛋白表达显著上调,MRTF-A质粒与bcl-2荧光素酶质粒共转染后bcl-2荧光素酶活性显著增加,然而,转染突变型bcl-2后MRTF-A的正向调节作用被消除。

结论

间充质干细胞移植可有效减少该大鼠MI模型中心肌细胞凋亡,并上调MRTF-A表达。随之上调的bcl-2表达可能参与了该模型中间充质干细胞移植的有益作用。

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