转化生长因子-β在骨髓间充质干细胞治疗实验性自身免疫性重症肌无力机制中的作用  

Role of TGF-β in Mechanism of Treatment of Experimental Autoimmune Myasthenia Gravis with Bone Marrow Stromal Cells

作　　者：刘江恒[1] 韩志娟[1] 周明言[1] 李娜[1] 刘静[1] 穆莉莉[1] 孔庆飞[1] 李呼伦[1] 

机构地区：[1]哈尔滨医科大学神经生物教研室黑龙江省神经生物学重点实验室,哈尔滨150081

出　　处：《中国生物制品学杂志》2010年第3期225-229,共5页Chinese Journal of Biologicals

基　　金：国家自然科学基金(30770665);哈尔滨市科技创新人才研究专项资金项目(2009RFXXS009);哈尔滨医科大学研究生创新基金(HCXB2009018)

摘　　要：目的探讨转化生长因子-β(TGF-β)在骨髓间充质干细胞(BMSCs)治疗实验性自身免疫性重症肌无力(EAMG)机制中的作用。方法分离培养健康Lewis大鼠BMSCs,并进行大量体外扩增;以大鼠来源的乙酰胆碱受体(R-AChR)2次免疫Lewis大鼠,建立EAMG模型;第2次免疫的同时,经尾静脉移植BMSCs,1×107个/只,依据Lennon评分标准,进行体重测量和临床体征评定。并通过体外实验进一步探讨TGF-β在治疗EAMG过程中的具体机制。结果BMSCs移植明显缓解了EAMG的临床症状,临床评分及体重变化差异均有统计学意义,表明治疗有效;体外实验结果显示,BMSCs能通过TGF-β的分泌影响AChR特异性Th17/Treg细胞亚群的分布及其相关因子的分泌,以anti-TGF-β抗体封闭后,这种调节作用在一定程度上被抑制。结论BMSCs通过细胞因子TGF-β,能在一定程度上调节AChR特异性Th17/Treg细胞亚群的平衡,从而起到治疗EAMG的作用。Objective To investigate the role of transformation growth factor（TGF）-β in treatment of experimental autoimmune myasthenia gravis（EAMG）with bone marrow stromal cells（BMSCs）.Methods The BMSCs of healthy Lewis rats were isolated,cultured and proliferated in a large quantity in vitro.The rat model of EAMG was established by immunizing Lewis rats twice with R-AChR.At the same time of the second immunization,each model rat was transplanted with 1 × 107 BMSCs,then weighed and evaluated for clinical physical sign according to the requirements for Lennon scoring.The role of TGF-β in treatment of EAMG was further explored by test in vitro.Results The transplantation with BMSCs relieved the clinical syndrome of EAMG significantly.The clinical scores and bodyweights of rats treated with BMSCs showed significant difference with those untreated,indicating curative effect of BMSCs.In vitro test showed that BMSCs influenced the distribution of AChR-specific Th17 /Treg lymphocyte subsets and the secretion of relevant cytokines by secreting TGF-β,which was inhibited at a certain degree after blocking of TGF-β with anti-TGF-β antibody.Conclusion BMSCs regulated the balance of AChR-specific Th17 /Treg lymphocyte subsets at a certain degree by TGF-β thus treat EAMG.

关 键 词：转化生长因子-Β 骨髓间充质干细胞 实验性自身免疫性重症肌无力 

分 类 号：R392.12[医药卫生—免疫学] R746.1[医药卫生—基础医学]