大鼠骨髓间充质细胞经SDF-1预处理后移植对急性心肌梗死的治疗效果

目的 探讨大鼠骨髓间充质细胞(BMSC)经基质细胞衍生因子-1(SDF-1)预处理后移植对急性心肌梗死(AMI)的治疗效果.方法 (1)全骨髓贴壁法培养大鼠BMSC;逆转录聚合酶链反应(RT-PCR)和免疫组织化学法检测BMSC趋化因子受体(CXCR4)基因的表达;将BMSC分别与10和100μg/L的SDF-1作用24 h后,在无氧、无血清条件下培养6 h,流式细胞仪和末端标记(TUNEL)法检测细胞凋亡率.(2)建立大鼠急性心肌梗死模型,将经100μg/L SDF-1预处理的BMSC和未经处理的BMSC植入大鼠梗死心肌周边,2周后采用超声心动图观察心脏功能的变化.结果 BMSC表达CXCR4基因;在无氧和无血清条件下,经SDF-1预处理的BMSC凋亡率与对照组比较明显降低(P<0.05),而经100 μg/L SDF-1预处理的BMSC凋亡率最低.成功建立大鼠急性心肌梗死模型;与未经处理的BMSC移植比较,经SDF-1预处理的BMSC移植后改善心肌梗死大鼠的心功能作用更为明显(P<0.05).结论 用SDF-1预处理大鼠BMSC能抑制其在无氧和无血清条件下的凋亡.用SDF-1预处理BMSC能增强其移植后治疗大鼠急性心肌梗死的效果.

Cellular transplant applied with rat bone marrow stromal cells preconditioned with stromal-derived factor 1 to treat acute myocardial infarction

Objective To investigate the effects of preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) on the levels of apoptosis of bone marrow stromal cells (BMSC) treated with hypoxia plus serum deprivation, and observe the therapeutic efficacy of cellular transplant with BMSC preconditioned with SDF-1 in rats with acute myocardial infarction. Methods BMSC were cultured with the whole marrow-adherence way. RT-PCR and immunohistochemistry were used to determine the expression of CXCR4. BMSC were incubated in medium for 24 h with 10 and 100 μg/L SDF-1 respectively, then treated with hypoxia plus serum deprivation for 6 h. The levels of apoptosis were detected by flow cytometry and TUNEL method. Acute myocardial infarction (AMI) model was established in SD rats, and BMSC preconditioned or non-preconditioned with SDF-1 were transplanted into border zone around infarct area, then heart function was measured after two weeks by ultrasonography. Results BMSC exhibited the CXCR4 expression. The number of apoptotic cells was significantly reduced in SDF-1 PC group than in control group (P<0.05), and 100μg/L SDF-1 PC group had the lowest level of apoptosis. AMI model was established successfully. Two weeks after BMSC transplant, significant improvement in cardiac function was observed in 100 μg/L SDF-1 PC group as compared with the non-PC group (P<0.05). Conclusions PC with the chemokine SDF-1 suppresses the apoptosis of BMSC treated with hypoxia plus serum deprivation. SDF-1 PC is a novel approach for enhancing therapeutic efficacy of cellular transplant in rats with AML