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目的利用经杆状病毒基因载体系统进行micro-dystrophin基因修饰后的脂肪干细胞(ADSCs)移植治疗Duchenne型肌营养不良症模型(mdx)鼠,探讨ADSCs移植治疗DMD的安全性及可行性。方法 Mdx鼠60只,分为mdx对照组(30只)和mdx移植组(30只);正常C57小鼠为C57对照组(30只)。体外分离培养小鼠ADSCs,利用杆状病毒基因载体进行micro-dystrophin基因修饰;将基因修饰后的ADSCs经尾静脉移植到mdx鼠体内。于移植后检测mdx鼠的运动功能(采用主动牵引实验和被动转棒实验)、血清CK水平、肌肉病理改变以及肌肉micro-dystrophin表达水平。结果经micro-dystrophin基因修饰的ADSCs移植后,能够重建mdx鼠的micro-dystrophin表达,一定程度上减轻并逆转肌肉的病理损害,进而降低血清CK水平,mdx鼠整体运动功能也有一定改善。结论 ADSCs治疗mdx鼠后,可部分重建模型鼠的dystrophin表达,改善肌肉的病理损害,表明ADSCs是有希望治愈DMD的方法之一。
Objective To investigate the safety and feasibility of ADSCs transplantation in the treatment of Duchenne muscular dystrophy (mdx) mice by transplantation of ADSCs transfected with micro-dystrophin gene by baculovirus vector system. Methods Sixty male Mdx mice were divided into three groups: the mdx control group (30 mice) and the mdx transplantation group (30 mice). The normal C57 mice were C57 control group (30 mice). ADSCs were isolated and cultured in vitro, and micro-dystrophin gene was modified by baculovirus gene vector. ADSCs modified by gene were transplanted via tail vein into mdx mice. The motor function of mdx mice (using active traction test and passive rotation stick test), serum CK level, muscle pathological changes and muscle micro-dystrophin expression were detected after transplantation. Results After transplanted with ADSCs modified with micro-dystrophin gene, the expression of micro-dystrophin in mdx mice could be reconstructed and the muscle pathological damage was reduced to a certain extent, and the level of serum CK was also decreased. The overall motor function of mdx mice was also improved. Conclusion ADSCs treatment of mdx mice, partial reconstruction of dystrophin expression in rat model to improve the pathological muscle damage, indicating that ADSCs is one of the promising ways to cure DMD.