微囊化牛肾上腺髓质嗜铬细胞脑内移植治疗偏侧帕金森病样猴的行为及神经生化效应
Xenotransplantation of microencapsulated bovine chromaffin cells into hemiparkinsonian monkeys
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摘要: 目的: 观察微囊化牛肾上腺嗜铬细胞(BCC)脑内移植对偏侧帕金森病(PD)样猴的行为和脑组织液中单胺类物质含量的影响;评价微胶囊的免疫隔离效果。方法: 以海藻酸钠-多聚赖氨酸-海藻酸钠(APA)为材料包裹BCC。右侧颈内动脉注射甲基-苯基-四氢吡啶(MPTP)诱发PD样猴模型。将微囊化、非囊化BCC或空微囊分别植入PD样猴右侧尾状核和壳核,观察PD样猴行为、尾状核及壳核微透析液中单胺类物质的变化。结果: 囊化组(n=6)和非囊化组(n=2)移植后1周开始PD样猴左侧上肢活动明显增加,阿朴吗啡(Apo)诱发的异常旋转次数减少。非囊化组猴在移植1~2个月后主动行为及Apo诱发的异常旋转圈数逐渐退回到移植前水平;而移植囊化BCC6只PD样猴的异常行为纠正效果,在观察的7个月内仍存在。空囊组(n=1) PD样猴异常行为无变化。移植前PD样猴右侧壳核、尾状核细胞外液中DA、DOPAC和HVA水平较左侧明显降低(P<0.05)。移植后2、7个月时,囊化组右侧壳核、尾状核细胞外液中DA、DOPAC和HVA水平较左侧明显降低(P <0.05)。移植后2、7个月时,囊化组右侧壳核、尾状核细胞外液中DA、DOPAC和HVA水平较移植前明显提高(P <0.05),但仍低于左侧的水平。结论: PD样猴脑内移植BCC后异常行为明显改善,微囊组的纠正效果明显优于非囊化组,其移植区DA及其代谢产生明显增加。APA微囊具有良好的免疫隔离作用,能明显延长BCC在异种脑内存活和发挥作用的时间。Abstract: Objective: To examine the effects of xenografts of microencapsulated bovine chromaffin cells (BCCs) on the rotational behavior of hemiparkinsonian monkey recipients and determine the content of monoamine neurotransmitters and their major metabolites in the neostriatum in hemiparkinsonian monkeys. Methods: The hemiparkinsonian model in monkeys was induced by a unilateral intracarotid injection of methyl-phenyl-tetrahydropyridine (MPTP).Unencapsulated BCCs,BCCs microencapsulated in alginate-polylysine-alginate (APA) membranes as well as empty m-i croencapsules were grafted into the neostriatum of the hemiparkinsonian monkeys. Results: Following the transplantation the hemiparkinsonian symptoms subsided and the number of rotations induced by apomorphine decreased for up to 7 months in the group of recipients grafted with microencapsulated BCCs,while only a temporary improvement (1~2 month) was detected in the recipients of the unencapsulated BCCs.No change was observed in the recipients of empty microencapsules.Dopamine and its metabolites were found considerably depleted in the MPTP-lesioned side versus the unlesioned side of the neostriatum in the hemiparkinsonian monkeys (P <0.05).The extracellular levels of them in the right putamen increased markedly 2months and 7months after the transplantation of microencapsulated BCCs as compared to pretransplantation levels (P <0.05). Conclusion: The results clearly indicate that the transplantation of immunoisolated BCCs can improve the parkinsonian symtoms and increase the content of dopamine and its metabolites for long periods of time in hemiparkinsonian monkeys.The method represents a promising aproach to the treatment of PD and merits further studies.
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