miRNA-451/MIF在帕金森病小鼠认知功能障碍中的保护作用  

Protective Effects of miRNA-451/MIF in Parkinson′s Disease Mice Model with Cognitive Impairment.

作　　者：陈嘉宁 李尤 高玉元[2] 聂坤[2] 王丽娟 Chen Jianing;Li You;Gao Yuyuan(School of Medicine,South China University of Technology,Guangdong 510000,China)

机构地区：[1]华南理工大学医学院,广州510000 [2]广东省人民医院神经科,广州510080

出　　处：《医学研究杂志》2021年第10期35-40,共6页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81671275,81974195);广东省重点领域研发计划项目(2018B030337001);广东省科技计划项目(2020A0505140006);广东省基础与应用基础研究基金资助项目(2019A1515110061)。

摘　　要：目的研究miRNA-451/MIF通路在帕金森病(PD)认知障碍中的作用及机制,为PD认知障碍提供治疗新思路和方法。方法腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)构建PD小鼠模型,通过脑立体定向注射干预PD小鼠模型脑组织中miRNA-451表达,采用Morris水迷宫对小鼠进行认知行为学评估,qPCR、免疫组化、尼氏染色检测干预前后脑组织miRNA-451/MIF分子表达、多巴胺能神经元细胞存活、海马区细胞形态。结果MPTP腹腔注射会引起小鼠认知行为受损(P<0.01),脑组织内miRNA-451表达增加(P<0.01),认知更差的小鼠miRNA-451表达更多(P<0.05)。人为降低miRNA-451表达后可以改善MPTP腹腔注射引起的认知功能受损(P<0.05),增加脑组织内MIF表达(P<0.05)并且缓解黑质多巴胺能神经元细胞受损(P<0.01),减少海马区神经元细胞的受损。结论miRNA-451/MIF可能参与PD认知障碍的发生及发展,干预miRNA-451/MIF表达可为治疗PD认知障碍提供新方法和新策略。Objective To investigate the role of miRNA-451/MIF and its downstream signaling pathway on cognitive impairment in Parkinson′s disease(PD),aiming to discover new therapeutic ideas of PD cognitive impairment.Methods PD animal model were constructed by intraperitoneal injection of MPTP.miRNA-451 antagomir was injected into lateral ventricle by a stereotactic microinjection to downregulate miRNA-451 expression.Cognition was evaluated by Morris water maze test.The expression of miRNA/MIF,the survival of dopaminergic neurons in substantia nigra,the damage of neurons in hippocampus were assessed by quantitative PCR,immunohistochemistry or Nissl staining.Results Intraperitoneal injection of MPTP could induced cognitive impairment in PD mice model(P<0.01).The expression of miRNA-451 increased in PD mice model(P<0.01)and the expression was higher in PD mice with worse cognition(P<0.05).Downregulation of miRNA-451 could improve cognition in PD mice model(P<0.05),increase the expression of MIF(P<0.05),alleviate the damage of dopaminergic neurons in substantia nigra(P<0.01)and the neurons in hippocampus.Conclusion miRNA-451/MIF may participate in the development of PD and PD cognitive impairment.Treatment targeting miRNA-451/MIF pathway may be effective to PD cognitive impairment.

关 键 词：帕金森病 认知功能障碍 miRNA-451 巨噬细胞移动抑制因子 

分 类 号：R741[医药卫生—神经病学与精神病学]