肝细胞生长因子基因修饰的骨髓间充质干细胞对扩心病大鼠心肌纤维化和凋亡的影响

目的通过移植人肝细胞生长因子（hHGF）基因修饰的骨髓间充质干细胞（MSCs）和未经修饰的MSCs来比较二者对扩张型心肌病（DCM）心力衰竭大鼠心功能的影响,并比较它们对心肌纤维化和凋亡的影响。方法 50只12周龄清洁级雄性SD大鼠随机抽取14只作为对照组,其余36只大鼠腹腔注射盐酸阿霉素制作DCM心力衰竭大鼠。存活大鼠（n=24）再随机平分为3组：DCM模型组、MSCs移植组和hHGF基因修饰的MSCs（MSCs-hHGF）移植组。经尾静脉移植干细胞4周后,分别检测左室收缩峰压（LVSP）、左室舒张末期压（LVEDP）、左室内压最大变化速率（±dp/dtmax）,然后比较各组心功能改变情况;免疫组化检测心肌hHGF含量;天狼猩红染色评价心肌胶原含量和TUNEL法检测心肌凋亡指数（AI）。结果与模型组相比,MSCs组和MSCs-hHGF组的左室收缩峰压（LVSP）均升高,左室舒张末期压（LVEDP）均降低,心肌胶原含量均降低,AI均下降;与MSCs组相比,MSCs-hHGF组LVSP升高,LV-EDP降低,心肌胶原含量降低,AI无明显差异。MSCs-hHGF组心肌hHGF含量显著高于其他各组,其他组间无差异。结论 MSCs-hHGF组比MSCs组能更加显著地改善DCM心力衰竭大鼠心功能,可能与MSCs-hHGF分泌的hHGF能够进一步抑制心肌纤维化有关;心功能的进一步提高不能归因于hHGF可能存在的抗心肌凋亡效应。

Effects of MSCs modified by hepatocyte growth factor on myocardial fibrosis and apoptosis of dilated cardiomyopathy rats

Objective To compare the effects of transplantation of bone marrow-derived meshenchymal stem cells （ MSCs） modified by human hepatocyte growth factor（ hHGF） gene （ MSCs-hHGF） and MSCs modified by nothing on heart function,myocardial fibrosis and apoptosis of rat model of dilated cardiomyopathy. Methods A total of 50 male SD rats （ 12-week-old） were included,of which 14 rats were randomly selected and served as control group. A model of dilated cardiomyopathy was induced by intraperitoneal injection of doxorubicin hydrochloride in the remaining rats （ n = 36）. The survivals of rats （ n = 24） were randomly divided into three groups,the DCM model group,the MSCs transplantation group and the MSCs-hHGF transplantation group. 4 weeks after caudal vein stem cells transplantation,left ventricle systolic pressures （ LVSP） ,left ventricular end-diastolic pressures （ LVEDP） and the maximum rate of change of left ventricular pressure,（ ± dp/dtmax） were evaluated so as to compare heart function among all groups. Immunohistochemical staining was used to examine the expression of hHGF in myocardial tissue. The myocardial collagen content was assessed by Sirius red staining,and myocardial apoptosis index（ AI） was detected by TUNEL straining. Results Compared to the DCM model group,LVSP and ± dp/dt max of both MSCs-hHGF group and MSCs group increased obviously,while their LVEDP,myocardial collagen content and AI decreased obviously. Compared to the MSCs group,LVSP and ± dp/dtmax of the MSCs-hHGF group further increased significantly,while its LVEDP、myocardial collagen content further decreased. However,the myocardial AI is similar between the two groups. The hHGF expression in myocardial tissue of the MSCs-hHGF group was much higher than other groups,there was no statistically significant difference on AI among three other groups. Conclusion The MSCs-hHGF group could further improve heart function of DCM heart failure rats than the MSCs group,which is probably associate with the secreted hHGF from MSCs-hHGF being able to inhibit myocardial fibrosis; the more significantly improved heart function in the MSCs-hHGF group is better than in the MSCs group could not be attributed to the potentially inhibiting myocardial apoptosis effect of hHGF.