骨髓干细胞移植治疗肌萎缩侧索硬化症转基因鼠的疗效  

Effect of Transplantation of Wild-type Bone Marrow Stem Cells in Mouse Model of Familial Amyotrophic Lateral Sclerosis

作　　者：黄慧[1] 张成[1] 赵翠萍[1] 姚晓黎[1] 席静[1] 

机构地区：[1]中山大学附属第一医院神经科,广州510080

出　　处：《中国医学科学院学报》2006年第4期562-566,共5页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(30170337;30370510);广东省自然科学基金(31693);卫生部临床学科重点项目(2001321)~~

摘　　要：目的 观察骨髓干细胞移植后肌萎缩侧索硬化症（ALS）模型鼠生存期和运动功能的变化。方法PCR法鉴定的6—9周龄ALS转基因阳性雌鼠（40只）分为ALS移植组（25只）和ALS对照组（15只），移植前5～7d给予5．5—6．5Gyγ射线预处理移植鼠；收取来自同窝正常雄鼠的全骨髓细胞，经尾静脉注射移植到移植鼠体内[（1—2）×10^7／只]，ALS对照组尾静脉注射无血清培养基；评估移植物抗宿主病（GVHD）表现，移植8周后PCR法检测ALS移植鼠血基因组Y染色体的性别决定基因（Sry基因）；与ALS对照组比较发病时间、生存期的改变，并以悬尾、转棒、转轮和牵引实验检测16—17周龄时两组ALS鼠的运动功能差别。结果部分移植鼠出现不同程度GVHD反应，GVHD总体评分1—2分，移植8周后检测移植鼠血基因组Sry基因结果呈阳性；ALS移植组比ALS对照组发病时间和生存期平均延后5周（P〈0．01）；16～17周龄时的悬尾、转棒、转轮和牵引实验检测结果显示移植组的运动功能比ALS对照组明显改善（P〈0．01）。结论经静脉移植的正常小鼠骨髓干细胞能在ALS转基因阳性鼠体内长期存活，并可改善模型鼠的生存期、发病时间和运动功能，提示骨髓干细胞移植可能改善ALS预后的临床治疗前景。Objective To determine the effects of wild-type mouse bone marrow stem ceils transplants on survival time and motor functions in the human mutant SOD1 -G93A mouse model of familial amyotrophic lateral sclerosis （ALS）. Methods Bone marrow stem ceils derived from the wild-type male mice were delivered intravenously into 25 ALS transgenic female mice （ carrying the human SOD1 gene with Gly 93 Ala mutation） that had been pretreated with 5.5-6.5 Gy γ-ray 5-7 days before. The onset time of limbs paralysis, lifespan and the graft versus host disease （GVHD） symptoms were observed in the treated group and statistically compared with control group of 15 media-injected ALS transgenic mice. The Sry gene （ sex determine region on the Y chromosome） were detected by polymerase chain reaction technique in the blood sample of treated female ALS mice after 8 weeks of transplantation. A series of animal motor tests including rotating rods, rotated wheel and extension reflex were performed in both two groups at the same age of 16-17 weeks to assess the mice survival motor functions. Results A few treated mice （ 7/25 ） had different clinical presentations of GVHD. The semi-quantity evaluation score of average GVHD among the treated ALS mice was not over 1-2. The detection of Sry gene on these treated female ALS group was positive. The average onsets of limb paralysis and survival time were prolonged for about 5 weeks. At the age of 16-17 weeks, the motor function in the treated group was significantly better than in the ALS control group （ P 〈 0. 01 ）. Conclusions Transplantation of wild-type mice bone marrow stem ceils can prolong survival in the recipient mice and ameliorate motor dysfunction. Intravenous administration of normal bone marrow stem cells may have therapeutic values for ALS.

关 键 词：肌萎缩侧索硬化症 小鼠 转基因模型 骨髓干细胞移植 

分 类 号：R746.4[医药卫生—神经病学与精神病学]