骨髓间充质干细胞移植对心力衰竭大鼠心功能的影响

目的探讨骨髓间充质干细胞（MSCs）对心衰大鼠心功能的影响及其机制。方法腹腔注射阿霉素（2mg／kg，每周1次，连续6周）至近交系F344大鼠体内，建立心衰大鼠模型。存活大鼠（32只）随机分为2组：心衰组（16只）和细胞移植组（16只）。分离纯化大鼠MSCs进行体外培养，予4，6-联脒-2-苯基吲哚（DAPI）进行标记；经股静脉注射MSCs或DMEM至心衰大鼠体内。细胞移植后4周，应用多导生理记录仪测量大鼠心功能；通过免疫组织荧光及化学染色，观察移植细胞存活情况，并计算血管数量；通过天狼猩红染色计算心肌胶原容积分数（CVF）和血管周围胶原面积（PVCA）。结果移植后4周，细胞移植组大鼠心肌组织见到DAPI标记的移植细胞存活，并表达心肌特异性抗原心肌肌球蛋白重链（β—MHC）。与心衰组相比，细胞移植组最大左室收缩末压（LVSP）、左室内压最大（最小）变化速率（LV＋dp／dtmax）均明显升高（P〈0．05），而左室舒张末压（LVDP）明显下降（P〈0．05）；细胞移植组左室血管数量明显高于心衰组（11．83±1．40）个比（7．78±1．39）个，P〈O．05]，细胞移植组左心室内膜CVF及PVCA明显低于心衰组（4．53±1．98比7．79±1．99，10．91±2．31比14．17±2．49，P〈0．05）。结论MSCs移植可改善心衰大鼠心功能，其机制可能与MSCs归巢至心脏，分化为心肌样细胞，并且促进血管新生、抑制心肌纤维化有关。

The effect of mesenchymal stem cell transplantation on the cardiac function in heart failure rats

Objective To observe the effect of intravenous transplantation of mesenchymal stem ceils （MSCs） on cardiac function in heart failure rats and its mechanism. Methods To establish rat model of heart failure, adriamycin was given intraperitoneally to F344 rats weekly at a dose of 2 mg/kg for 6 weeks. The survival rats（n=32） were then randomly divided into two groups, heart failure group（n=16） and cell transplantation group （n= 16）. MSCs were isolated from F344 rats and cultured in vitro and labeled with（4,6-diamidino-2-phenylindele, dihydrochloride, DAPI） before transplantation. DAPI-labeled MSCs（3×10^6 cells） or DMEM were injected into heart failure rats via femoral vein. Four weeks after the transplantation, cardiac function was evaluated with hemedynamic measurement. Hearts were harvested and observed with fluorescence microscope to identify whether MSCs can migrate into impaired heart, the vessel numbers were calculated by VWF immunohistochemistry. The interstitial collagen volume fraction （CVF） and perivascular circumferential collagen area （PVCA） were calculated by Picrosirius red staining. Rusults Four weeks after transplantation, MSCs labeled with DAPI were found and expressed cardiac specific antigen, 13 myosin heavy chain （β-MHC） in the myocardium of cell transplantation group. Hemodynamic parameters such as LVSP, LV ＋dP/dt and LV -dP/dt were increased but LVDP was decreased in the cell transplantation group when compared with heart failure group （P〈0.05）. Vessel number was significantly increased in the cell transplantation group when compared with heart failure group （11.83±1.40 vs 7.78±1.39,P〈0.05）.CVP and PVCA of left heart ventricle were significantly decreased in the cell transplantation group when compared with heart failure group（4.53±1.98 vs 7.79±1.99,10.91±2.31 vs 14.17±2.49,P〈0.05）. Conclusion MSCs transplantation can improve cardiac function in this rat model of heart failure , and the mechanism may be that MSCs migrate into impaired heart and differentiate into cardiomyocyte and improve myocardial blood supply, as well as MSCs inhibit myocardial fibrosis.