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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。
Objective To compare the effects of hGGF gene-modified MSCs and unmodified MSCs on cardiac function in rats with dilated cardiomyopathy (DCM) Their effects on myocardial fibrosis and apoptosis were compared. Methods Fifty 12-week-old male Sprague-Dawley rats were randomly divided into control group, and the other 36 rats were injected intraperitoneally with doxorubicin hydrochloride to make DCM heart failure rats. Survival rats (n = 24) were randomly divided into 3 groups: DCM model group, MSCs transplantation group and hHGF gene-modified MSCs (MSCs-hHGF) transplantation group. Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximal rate of change of left ventricular pressure (± dp / dtmax) were measured after transplantation of stem cells through tail vein for 4 weeks. The content of hHGF in myocardium was detected by immunohistochemistry. The content of myocardial collagen was measured by Sirius red staining and the apoptosis index (AI) was detected by TUNEL. Results Compared with model group, LVSP and LVEDP were decreased in MSCs group and MSCs-hHGF group, while collagen content and AI in both MSCs-hHGF group were decreased; Compared with MSCs-hHGF group, LVSP increased, LV-EDP decreased, myocardial collagen content decreased, AI had no significant difference. MSCs-hHGF group myocardial hHGF content was significantly higher than the other groups, no difference between the other groups. Conclusions MSCs-hHGF group can significantly improve cardiac function in rats with DCM heart failure than MSCs group, which may be related to the fact that hHGF secreted by MSCs-hHGF can further inhibit myocardial fibrosis. Further improvement of cardiac function can not be attributed to the possible presence of hHGF Anti-myocardial apoptosis effect.