骨髓间充质干细胞移植治疗心力衰竭

Therapy of Heart Failure Rats with Mesenchymal Stem Cell Transplantation

目的探讨骨髓间充质干细胞移植对阿霉素诱导的心力衰竭大鼠心功能的影响。方法无菌条件下取8周龄F344大鼠的股骨和胫骨,获得骨髓间充质干细胞(MSCs),在体外纯化、扩增后,用5-溴-2’脱氧尿苷(BrdU)进行标记,然后注射到心力衰竭模型细胞移植组和对照组大鼠的心肌组织内,细胞移植后4周,采用生理记录仪测量3组大鼠的心功能,处死动物,心脏切片行免疫组化了解移植细胞在受体心脏的存活情况。结果细胞移植后4周,细胞移植组大鼠死亡率为6.2%,明显低于假细胞移植组12.5%(P<0.01);在受体大鼠的心脏切片上有BrdU标记的移植细胞存活。心功能测定显示:与对照组相比,细胞移植组最大左室收缩末压(LVSP)、心率(HR)、左室内压最大(最小)变化速率(LV±dp/dtmax)均明显下降(P<0.01),而左室舒张末压(LVDP)明显升高(P<0.01);与对照组相比,细胞移植组大鼠的LVSP、HR、LV±dp/dtmax均有明显升高(P<0.01),而LVDP明显降低(P<0.01);与假移植组相比,细胞移植组大鼠的HR、LV±dp/dtmax仍有明显下降(P<0.01),而LVDP明显升高(P<0.01)。结论MSCs移植可有效改善阿霉素诱导的扩张型心力衰竭大鼠的心功能,减少心力衰竭大鼠的死亡率。

Objective Explore the effect of mesenchymal stem cell transplantation on cardiac function in rats with adriamycin（Adr）-induced heart failure.Methods MSCs were isolated from 8-week old F344 rats and cultured in vitro.Cells at the third passage were identified with a flow cytometer and labeled with（5-Bromo-2＇-Dexuuridine,BrdU）before transplantation.BrdU-labeled MSCs（3×10^6 cells）was transplanted into rats（the transplantation group and the sham transplantation group,respectively）via femoral vein.Four weeks after the transplantation,cardiac function was evaluated using physiological recorder.Hearts were harvested and analyzed by immunohistochemistry to identify the transplanted BrdU-labeled cells.Results Four weeks after transplantation：the mortality of transplantion group was 6.2%,significantly lower than 12.5% in sham transplantation group（P〈0.01）;BrdU-labeled transplanted MSCs could be found in the hearts of the recipients.Hemodynamic measurements showed that Adr caused a significant decrease in LVSP,heartrate,LV±dp/dtmax and an increase in LVDP in the sham transplantation group（P〈0.01）,compared with the normal control group.Mesenchymal stem cell transplantation significantly improved hemodynamic parameters：LVSP,heart rate,LV±dp/dtmax and LVDP,compared with those in the sham transplantation group,but still significantly lower than that in the normal control group（P〈0.01）.Conclusion Mesenchymal stem cell transplantation significantly improve cardiac function and survival in rats with Adr-induced heart failure.