摘要
目的探究miR-124-5p对帕金森大鼠脑黑质区小胶质细胞极化的作用及机制。方法Wistar雄性大鼠随机分为假手术组(Sham组)、帕金森组(PD组)和agomiR-124-5p组(agomiR组),每组10只。阿朴吗啡转诱导实验和异常不自主评分评价大鼠神经行为学;免疫荧光检测大鼠脑黑质TH阳性多巴胺神经元数量及M1型和M2型小胶质细胞数量;ELISA检测大鼠脑黑质炎症因子水平;生物信息学数据库预测与miR-124-5p结合的靶基因,双荧光素酶报告基因实验验证;qRT-PCR和Western blot检测大鼠黑质区STAT1表达。结果miR-124-5p改善帕金森大鼠神经行为学,增加大鼠脑黑质区神经元数量,降低M1型小胶质细胞分泌的炎症因子水平,增加M2型小胶质细胞分泌的炎症因子水平,驱动M2型小胶质细胞极化,miR-124-5p靶向结合STAT1,并降低帕金森大鼠脑黑质区STAT1表达。结论miR-124-5p通过靶向抑制STAT1表达,驱动帕金森大鼠小胶质细胞向M2型极化,改善脑损伤。
Objective To explore the effect and mechanism of miR-124-5p on microglia polarization in the substantia nigra of Parkinson’s disease rats.Methods Wistar male rats were randomly divided into sham group(Sham group),Parkinson’s disease group(PD group)and agomiR-124-5p group(agomiR group)with 10 rats in each group.The neurobehavior of rats was evaluated by the apogaline-induced transformation experiment and the abnormal involuntary score(AIM).The number of TH positive dopamine neurons and the number of M1-type and M2-type microglia in the substantia nigra were detected by immunofluorescence.The levels of inflammatory factors in the substantia nigra were detected by ELISA.The target genes combined with miR-124-5p were predicted by bioinformatics database and verified by dual luciferase reporter gene experiment.The expression of STAT1 in the substantia nigra was detected by qRT-PCR and Western blot.Results miR-124-5p improved the neurobehavior of Parkinson’s disease rats,increased the number of neurons in the substantia nigra,decreased the level of inflammatory factors secreted by M1-type microglia,increased the level of inflammatory factors secreted by M2-type microglia,and drove the polarization of M2-type microglia.miR-124-5p targeted to STAT1,and down-regulated the expression of STAT1 in the substantia nigra of Parkinson’s disease rats.Conclusion miR-124-5p drives M2-type polarization of microglia in Parkinson’s disease rats and improves brain damage by targeting STAT1.
作者
任占秀
张贺敏
付钟果
何秋
REN Zhan-xiu;ZHANG He-min;FU Zhong-guo;HE Qiu(Department of Neurology,Liaoning Provincial People's Hospital,Shenyang 110016,China)
出处
《解剖科学进展》
CAS
2022年第4期405-408,412,共5页
Progress of Anatomical Sciences
基金
辽宁省自然科学基金(2018011490-301)
