多轨迹神经微移植策略在亨廷顿病大鼠模型移植治疗研究中的应用

Application of Multi-track Micro-transplantation in Cell Replace Therapy in a Rat Model of Huntington's Disease

目的:探讨单轨迹和多轨迹神经微移植技术在亨廷顿病(HD)大鼠毁损模型中的作用及机制。方法:SD大鼠59只,分为对照组(n=15)、毁损组(n=14)、多轨迹(MT)移植组(n=15)和单轨迹(ST)移植组(n=15)。对照组不予任何处理,其它3组实施单侧纹状体毁损手术,其中MT或ST移植组分别由MT或ST注射移植相同数量的胎龄15d的鼠胎神经节隆起处细胞。移植4个月后行组织学评估及多巴胺和cAMP调节的磷蛋白(DARRP-32)阳性细胞计数。结果:MT移植组计数的DARRP-32阳性神经元约为ST移植组的2倍。移植物体积、DARPP-32碎片体积和新生多巴胺能神经支配体积在2组中未见统计学差异。结论:MT神经微移植方式可以增加新生纹状体神经元的数量,其机制可能是移植物-宿主接触面积的增大使得移植物更强地暴露于宿主环境诱导因素之下。

Objective：To investigate the application of single-track（ST） and multi-track（MT） micro-transplantation in cell replace therapy in a rat model of Hunting＇s disease（HD）.Methods：Fifty-nine SD rats were divided into groups control（n=15）,lesion（n=14）,MT（n=15） and ST（n=15）.The controls were not treated,and the other 3 groups were given lesion surgery of unilateral striatum.The unilaterally QA-lesioned rat striatum in MT and ST groups were implanted by cells derived from the whole ganglionic eminence of 15 d rat embryos in MT or ST respectively.After 4 months of transplantation,the animals in the 4 groups were evaluated histologically.Results： Nearly two-fold increase of DARRP-32 positive striatal-like neurons was observed in the MT group compared to the ST group.However,the volumetric values for overall volume,DARPP-32 positive patches and dopaminergic projection zones showed no difference between the both groups.Conclusion：Distribution of fetal striatal tissue in multiple submicroliter deposits results in an increase of striatal-like neurons,potentially due to the enlargement of the graft-host border area intensifying the graft＇s exposure to host derived factors.