摘要
目的 研究骨髓干细胞移植治疗Duchenne型肌营养不良鼠(dystrophin/utrophin gene double knock-outmice,dko鼠)的运动功能改善情况。方法 获取4～5周龄C57BL/6鼠的骨髓干细胞,体外培养3 d,以1.0×10~7/只静脉移植到经7Gy γ射线预处理的dko鼠(7～8周龄)。8～9周后,检测移植鼠运动功能、肌电图及肌肉组织dystrophin蛋白表达情况。结果 骨髓干细胞移植8～9周后,11只dko鼠牵引运动坠落次数为(3.09±2.47)次,与对照组(非移植组)dko鼠(16.78±3.6)次比较,有显著性差异;肌电图指标中,动作电位时限和最大收缩电位波幅分别为(4.99±1.62)ms,和(2872±1474.33)μV,与对照组(3.69±0.40)ms和(1210.00±551.00)μV比较,有显著改善;其肌肉组织有7％肌纤维表达了dystrophin蛋白。结论 静脉移植同种、同系鼠骨髓干细胞后,dko鼠的运动功能、电生理有了显著改善;其部分骨骼肌细胞有缺失蛋白的表达。提示干细胞移植治疗DMD有较理想的前景。
Objective Study the improvement of locomotive faculty of dystrophin/utrophin gene double knock-out mice (dko mice) by transplanting bone marrow stem cells. Methods The bone marrow stem cells of C57BL/6 mice (4-to 5-weeks age)were cultured in vitro for three days, before transplanted intravenously (1.0×10~7 for each)into 11 dko mice (7-to 8-weeks age ). The dko mice were irridiated with 7Gy γ-ray before transplantation. 8-9 weeks after transplantation, the locomotory function, electromyography items and expression of dystrophin in transplanted mice and controls were observed. Results 8-9 weeks after transplantation, the dropping times of hauling wire were 3.09 ± 2.47, compared with that of the control dko mice(16.78 ± 3.60), there are distinct differences. About electromyography items, the duration of active potential and amplitude of maxim contractions were (4.99 ± 1.62)ms and(2872±1474.33) μV, compare with those of control dko mice(3.69 ± 0.40) ms and(1210.0 ± 551.0) μV, respectively, about 7% fibers of the muscle tissue of transplanted dko mice expressed dystrophin protein. Conclusions 8-9 weeks after transplanted with homology bone marrow stem cells, the locomotive function and electromyography items of transplanted dko mice were obviously improved, and about 7% muscle tissue fibers of the mice expressing dystrophin protein were observed. It suggested that there is an ideal prospect for DMD therapy with bone marrow stem cells transplantation.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2003年第2期160-163,共4页
Acta Academiae Medicinae Sinicae
基金
△国家自然科学基金(30170337
39870804)
广东省自然科学基金(970061)
教育部骨干教师资助项目(20002349)
卫生部临床学科重点项目(2001321)资助
关键词
肌营养不良症
dko鼠
骨髓干细胞移植
蛋白表达
Duchenne muscular dystrophy
dystrophin/utrophin gene double knock-out mice
stem cells transplantation
locomotive function
