两类抗精神病药对脱髓鞘小鼠模型髓鞘修复的影响

Effects of two antipsychotics on remyelination in demyelinated mouse model

摘要目的：探讨抗精神病药物对双环己酮草酰二腙（CPZ）诱导的慢性脱髓鞘动物模型中髓鞘修复的作用。方法：持续给予CPZ喂养12周诱导小鼠慢性脱髓鞘模型，采用快蓝染色、髓鞘碱性蛋白（MBP）免疫组织化学显色等方法检测各组髓鞘变化，观察典型性抗精神病药氟哌啶醇和非典型性抗精神病药喹硫平对髓鞘修复的作用。通过免疫组织化学标记少突胶质前体细胞（OPCs）标志物Olig2，比较药物对OPCs的影响。结果：氟哌啶醇可以阻止髓鞘的自发性修复；喹硫平能促进慢性髓鞘再生的进程。在髓鞘修复过程中氟哌啶醇使OPCs数目减少；喹硫平可以促进OPCs增生。结论：在脱髓鞘模型中，氟哌啶醇抑制髓鞘自发修复，喹硫平可以促进髓鞘的慢性修复，其机制可能与两种药物对OPCs的不同作用有关。OPCs可能是抗精神病药治疗的靶点。

Objective： To investigate the effects of antipsychoties on remyelination in cuprizone-induced chronic demyehnatea mouse model. Methods： C57B1/6 mouse model of demyelination was established by using a diet supplemented with 0.2G cuprizone for 12 weeks. Luxol fast blue staining and MBP immunostaining were used to detect demyelination and remyelination in the models treated with a typical antipsychotic haloperidol and an atypical antipsychotic quetiapine. Oligodendrocyte progenitor cells （OPCs） were identified and measured by OPCs marker Olig2 treated with antipsychotics. Results： HaloperidoI delayed the progress of spontaneous remyeliantion, while quetiapine promoted the progress of spontaneous remyeliantion in chronic demyelination model. In addition, haloperidol decreased the number of Olig2 positive cells, while quetiapine increased the number of Olig2 positive cells in chronic demyelination model. Conclusion： Haloperidol delays the progress of spontaneous remyeliantion while quetiapine promotes the progress of spontaneous remyeliantion in chronic demyelination model. The mechanism may be due to the different effects of these two kinds of antipsychotic on OPCs. Therefore, OPCs may be a potential target of antipsyehotic medication.