自体间充质干细胞植入促进大鼠衰竭心肌生长因子表达、改善心室重构和心功能

Autologous mesenchymal stem cell implantation promotes myocardial expressions of growth factors and improves cardiac function in failing rat hearts

目的动物实验与临床应用显示，间充质干细胞（MSCs）改善心室重构和心功能，但MSCs这种作用的机制还不清楚。方法从大鼠自体股骨骨髓抽取并培养MSCs，用灼伤大鼠心室游离壁的方法制作慢性心力衰竭（CHF）模型，心肌损伤坏死5d后分别在坏死边缘区和远隔区植人自体MSCs。结果10周后与假手术组相比，CHF组大鼠在瘢痕边缘区心肌细胞核分裂指数、毛细血管密度及胰岛素样生长因子1（IGF-1）、肝细胞生长因子（HGF）和血管内皮生长因子A（VEGF-A）的表达显著增加（P〈0．01）；而在远隔区，以上指标显著下降（P〈0．05或P〈0．01）。与CHF组相比，自体MSCs植入（CHF＋MSCs组）显著增加了远隔区IGF-1、HGF及VEGF-A的表达，进一步增加了边缘区以上因子的表达（P〈0．05或P〈0．01），同时这两区的心肌细胞核分裂指数及毛细血管密度显著增加（P〈0．05或P〈0．01）。自体MSCs植入使CHF瘢痕边缘区胶原纤维百分比显著减少而心肌纤维百分比显著增加，心室重构和心功能显著改善。结论自体MSCs植入促进大鼠衰竭心肌生长因子表达，这种作用部分地促进了心肌和血管的再生，因此改善了心室重构和心功能。

Objective To explore the underlying mechanism of mensenchymal stem cells （MSCs） transfer induced cardiac function improvement in failing hearts. Methods Congestive heart failure （CHF） was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization. Results Ten weeks later, eardiomyoeyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 （IGF-1）, hepatocyte growth factor （HGF） and vascular endothelial growth factor （VEGF） were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats （all P 〈0. 05 vs. sham）. Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated （P 〈 0. 05 or P 〈 0. 01 vs. CHF）, and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs （P 〈0. 05 or P 〈0. 01 vs. CHF）. Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too. Conclusion Autologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.