低氧诱导因子-1α基因修饰后的成肌细胞移植治疗心肌梗死的研究

目的评价低氧诱导因子-1α(HIF-1α)基因修饰骨骼肌成肌细胞(SkMs)治疗心肌梗死的可行性及其疗效。方法将71只Wister大鼠采用结扎冠状动脉左前降支制备心肌梗死模型,通过局部注射法将细胞植入心肌梗死区域。其中将制膜成功的42只成活大鼠随机分为假手术组(SO组,6只)、注射培养液组(DMEM组,6只)、移植SkMs组(SkMs组,10只)、移植感染了携带HIF-1α空载体腺病毒的SkMs组(Ad/GFP组,10只)和移植感染了携带HIF-1α基因腺病毒的SkMs组(Ad/HIF-1α组,10只)。术后28天用免疫组织化学法和血流动力学评价治疗效果。结果28天后SkMs组、Ad/GFP组和Ad/HIF-1α组大鼠梗死心肌周围血管新生明显,以Ad/HIF-1α组最为显著(P<0.05),且胶原沉积最少;SkMs组、Ad/GFP组和Ad/HIF-1α组大鼠左心室收缩功能好转,Ad/HIF-1α组最为显著(P<0.05)。结论HIF-1α基因修饰后的SkMs移植较单纯成肌细胞移植是治疗心肌缺血更为有效的方法。

Research on treatment of acute myocardial infarction with transplanting skeletal myoblasts transfected with HIF-1α gene

Objective To assess the feasibility and efficacy of skeletal myoblasts transfected with hypoxia-inducible factor(HIF)-1α gene in treatment of myocardial infarction.Methods Myocardial infarction was created in 42 rats by means of coronary artery ligation.The rats were randomly allocated to sham operation group(n=6) and groups receiving in-scar injection of culture medium(n=6),skeletal myoblasts(n=10),skeletal myoblasts transfected with an empty vector(n=10) or active HIF-1α(n=10).After 28 d,left ventricular function was assessed by left ventricular systolic pressure(LVSP) and ±dP/dtmax.Angiogenesis was assessed by immunohistochemistry and reduction of fibrosis was displayed by Picrosirius red stain.Results Injection of skeletal myoblasts alone or combined with either the empty vector or active HIF-1α improved left ventricular function,including increase in the number of capillaries and reduction of fibrosis.The most striking change occurred in the skeletal myoblasts transfected with active HIF-1α group in which ±dP/dtmax increased dramatically compared with control group(P<0.05).Conclusion Induction of angiogenesis is an effective means for potentiating the functional benefits of myoblast transplantation,and HIF-1α can successfully achieve this goal.