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目的观察携带人肝细胞生长因子基因修饰的骨髓间充质干细胞(MSC-hHGF)对心力衰竭模型大鼠心肌纤维化影响。方法 50只12周龄清洁级雄性SD大鼠[体质量(200±10)g]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心力衰竭模型,存活大鼠(n=24)再随机平分为3组:模型组、骨髓间充质干细胞(MSC)组和MSC-hHGF组。采用密度梯度离心-贴壁培养法获取SD大鼠的MSC,Ad-hHGF转染HGF到MSC,ELISA检测hHGF在该细胞的表达情况。腹腔注射阿霉素建立扩张型心肌病心力衰竭大鼠模型。细胞移植后4周,用生物信号采集系统检测心功能,免疫组化检测左室心肌组织HGF表达水平,天狼猩红染色评价心肌纤维含量,偏振光显微镜分析瘢痕区Ⅰ型胶原表达情况。结果与模型组相比,MSC组的左室收缩峰压(LVSP)[(41.1±3.7)比模型组(33.2±1.4)mmHg,P<0.05]升高,MSC组的左室舒张末期压(LVEDP)[(15.7±1.3)比模型组(19.5±2.1)mmHg,P<0.05]降低;与MSC组相比,MSC-hHGF组LVSP[(49.6±6.1)比MSC组(41.1±3.7)mmHg,P<0.05]升高;MSC-hHGF组LVEDP[(8.7±1.1)比MSC组(15.7±1.3)mmHg,P<0.05]降低。MSC-hHGF组心肌组织Ⅰ型胶原含量与模型组比降低,但是与对照组比没明显差异。结论 MSC-hHGF可明显改善心力衰竭大鼠心功能和心肌纤维化。
Objective To observe the effect of human hepatocyte growth factor-modified bone marrow mesenchymal stem cells (MSC-hHGF) on myocardial fibrosis in rats with heart failure. Methods Fifty male Sprague-Dawley (SD) rats of 12 weeks of age [body weight (200 ± 10) g] were randomly selected as the control group. The remaining 36 rats were intraperitoneally injected with doxorubicin hydrochloride to make heart failure model and survived in rats n = 24) were randomly divided into 3 groups: model group, bone marrow mesenchymal stem cells (MSC) group and MSC-hHGF group. The MSCs of SD rats were obtained by density gradient centrifugation-adherent culture. HGF was transfected into MSC by Ad-hHGF, and the expression of hHGF in the cells was detected by ELISA. Intraperitoneal injection of doxorubicin to establish dilated cardiomyopathy rat model of heart failure. Four weeks after cell transplantation, cardiac function was measured by a biosignal acquisition system. HGF expression in left ventricular myocardium was detected by immunohistochemistry, myocardial fiber content was assessed by Sirius red staining, and type Ⅰ collagen expression was analyzed by polarized light microscopy. Results LVSP in MSC group [(41.1 ± 3.7) vs that in model group (33.2 ± 1.4) mmHg, P <0.05] was significantly higher than that in model group. The left ventricular end-diastolic pressure LVEDP) was significantly lower in MSC-hHGF group than in MSC group (49.6 ± 6.1 vs 41.1 ± 3.7 mmHg, P <0.05) , P <0.05]. LVEDP [(8.7 ± 1.1) vs MSC group (15.7 ± 1.3) mmHg, P <0.05] decreased in MSC-hHGF group. Compared with the model group, the content of collagen type Ⅰ in MSC-hHGF group decreased, but there was no significant difference between the model group and the control group. Conclusion MSC-hHGF can significantly improve cardiac function and myocardial fibrosis in rats with heart failure.