The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning
The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning
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缺氧预处理增强间充质干细胞移植对缺血心肌的抗凋亡作用。
DOI：
10.1016/s0828-282x(09)70094-7
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发表时间：
2009-06-01
影响因子：
6.2
通讯作者：
Wang, Jian-an
中科院分区：
文献类型：
--
作者：
He, Aina;Jiang, Yun;Wang, Jian-an
背景：心肌梗死后早期即发生心肌细胞凋亡。方法：采用Dulbecco改良的Eagle's培养液（对照组）、MSCs和AP-MSCs培养心肌细胞，观察缺氧预处理（AP）对MSCs抗凋亡作用的影响。凋亡心肌细胞用膜联蛋白V异硫氰酸荧光素（BioVision，USA）染色，通过荧光显微镜观察并通过流式细胞术分析。在体内，通过永久性结扎冠状动脉左前降支在Sprague-Dawley大鼠中产生MI，并且在MI后一周随机向左心室注射Dulbecco改良Eagle培养基、MSC或AP-MSC。移植后1周采用末端脱氧核苷酸转移酶介导的2 '-脱氧尿苷5'-三磷酸缺口末端标记法检测梗死周围心肌细胞凋亡率。移植后4周通过超声心动图评估心脏功能。移植后1周和4周，用苏木精-伊红染色法测量移植物的大小。结果：MSCs和AP-MSCs均能显著减少缺氧/复氧和心肌梗死诱导的心肌细胞凋亡，增加Bcl-2/Bax蛋白比值，降低cys-aspartic acid protease-3的表达。结论：MSCs对心肌梗死具有上级作用。通过防止心肌细胞凋亡和All增强了MSCs的心脏保护作用。
BACKGROUND: Cardiomyocyte apoptosis takes place at an early stage after myocardial infarction (MI). Therapy with mesenchymal stem cells (MSCs) is reported to reduce apoptosis.OBJECTIVES: To determine whether anoxic preconditioning (AP) could enhance the antiapoptotic effect of MSCs.METHODS: Cultured cardiomyocytes were created With Dulbecco's modified Eagle's medium (as a control), MSCs or AP-MSCs, and were exposed to hypoxia/reoxygenation. Apoptotic cardiomyocytes were stained with Annexin V fluorescein isothiocyanate (BioVision, USA), visualized by fluorescence microscopy and analyzed by flow cytometry. In vivo, MI was produced in Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery and the left ventricles were randomly injected with Dulbecco's modified Eagle's medium, MSCs or AP-MSCs one week after MI. The cardiomyocyte apoptotic rate in peri-infarcted areas was assessed by terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labelling assay one week after transplantation. Cardiac function was assessed by echocardiography four weeks after transplantation. Infarct size was measured by hematoxylin and eosin staining one and four weeks after transplantation. The expression of Bcl-2, Bax protein and cleaved cysteine-aspartic acid protease-3 was analyzed by Western Not techniques.RESULTS: Cardiomyocyte apoptosis (both induced by hypoxia/reoxygenation and MI) was significantly reduced by treating with MSCs and AP-MSCs, the Bcl-2 to Bax protein ratio was increased and cleaved cysteine-aspartic acid protease-3 was decreased. AP-MSCs were Superior to MSCS.CONCLUSIONS: MSCs protected the infracted heart. by preventing cardiomyocyte apoptosis and All enhanced the cardioprotective effects of MSCs.