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目的采用2-脱氧5氮杂胞苷(5-aza-2’-deoxycytidine,5-aza-CdR)诱导的骨髓间充质干细胞(MSCs)经尾静脉移植入不同时期的心肌梗死(MI)后心衰大鼠中,观察其向病损心肌的趋化作用及其在局部分布的特点,探讨其对心肌α-肌球蛋白重链(α-MHC)mRNA表达的影响。方法培养Wistar大鼠的MSCs,用0·3μmol/L的5-aza-CdR两次诱导第2代的MSCs。用溴氮胞苷(BrdU)标记后,经尾静脉植入MI后不同时期的心衰大鼠中,实验分为MI1d、8d、3周、1月后移植组及MI3周、1月后DMEM假移植组。采用免疫组化染色法检测移植后3d及1月的MSCs在大鼠心肌中的分布情况,并用RT-PCR检测移植1月后MI局部α-MHCmRNA水平的变化。结果在MI后不同时期(1d内、8d、3周、1月),通过尾静脉给予相同数量的MSCs,3d后在各组大鼠的心肌中均发现抗BrdU+的移植细胞。移植的MSCs主要分布在心肌受损区域,分布特点与移植时心肌的病理特点有一定的关系。急性、亚急性期,有较多的移植细胞,与自身细胞均匀分布。进入慢性期,移植细胞沿着纤维方向线样排列,呈团簇样分布,数目较急性期减少。移植后1月,各组大鼠心脏中仍有抗BrdU+的移植细胞,移植细胞分布的特点与移植后3d所观察的结果相似。研究发现,MI区域rattusα-MHCmRNA的表达,与MI3周移植的MSCs相比,在MI1d或8d后移植,差异无显著性。MI3周后移植MSCs,rattusα-MHCmRNA的表达较DMEM假移植组有明显提高(P<0.01),但在MI1月后移植与假移植组差异无显著性。结论在不同的MI时间段经尾静脉植入MSCs,其能向心肌趋化,主要分布在心肌的受损区域,分布特点与移植时心肌的病理特点有关。MI后早期给予MSCs移植,更有利于提高区域的表达
OBJECTIVE: To investigate the effects of 5-aza-2-deoxycytidine (5-aza-CdR) -induced MSCs transplanted into caudal vein on myocardial infarction (MI) To observe the chemotaxis and its distribution in myocardium of rats with heart failure, and to investigate its effect on myocardial α-MHC mRNA expression. Methods MSCs of Wistar rats were cultured and MSCs of the second generation were induced twice with 0-3 μmol / L 5-aza-CdR. The rats were divided into three groups: MI1d, 8d, 3weeks, transplantation group and MI3weeks after 1 month, DMEM after 1 month Fake transplantation group. Immunohistochemical staining was used to detect the distribution of MSCs in the myocardium of rats at 3d and 1 month after transplantation. The changes of MI local α-MHC mRNA level were detected by RT-PCR. Results The same number of MSCs were given via tail vein at different time points (1d, 8d, 3 weeks and 1 month). After 3 days, anti-BrdU + transplanted cells were found in the myocardium of rats in each group. Transplanted MSCs are mainly distributed in the damaged area of myocardium, the distribution characteristics of myocardial MSCs transplantation has a certain relationship between the pathological characteristics. Acute, subacute period, there are more transplanted cells, with their own cells evenly distributed. Into the chronic phase, the transplanted cells along the fiber direction of line-like arrangement, cluster-like distribution, the number of less than the acute phase. At 1 month after transplantation, there were still anti-BrdU + transplanted cells in the heart of each group. The characteristics of the transplanted cells were similar to those observed after 3 days of transplantation. The study found that, MI area rattusα-MHC mRNA expression, compared with MI3-week MSCs transplantation, MI1d or 8d after transplantation, the difference was not significant. After 3 weeks of MI transplantation, the expression of rattusα-MHC mRNA was significantly increased (P <0.01) compared with that of DMEM transplantation group. Conclusions MSCs are implanted into caudal vein in different MI periods, which can induce myocardial chemotaxis, which mainly distributes in the damaged area of myocardium. The distribution of MSCs is related to the pathological features of myocardium during transplantation. MS transplantation of MSCs early, more conducive to improve the expression of the region