| 王丹蕾，薛峥，覃奇雄，李静怡，赵经纬，毛志娟.miR-218-5p改善帕金森病小鼠多巴胺能神经元变性[J].神经损伤功能重建,2022,17(5):249-253 |
| miR-218-5p改善帕金森病小鼠多巴胺能神经元变性 |
| MiR-218-5p Ameliorates Degeneration of Dopaminergic Neurons in MPTP-Induced Mice |
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| DOI： |
| 中文关键词: 帕金森病 多巴胺能神经元 miR-218-5p Wnt/β-catenin信号 |
| 英文关键词: Parkinson’s disease dopaminergic neurons miR-218-5p Wnt/β-catenin signaling |
| 基金项目:国家自然科学基金
重大研究项目（No.
91849121）；
国家自然科学基金
青年科学基金（No.
81901303） |
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| 中文摘要: |
| 目的：探索miR-218-5p对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的急性帕金森病（PD）模型小鼠
黑质多巴胺能神经元的保护作用及其可能机制。方法：18只8周雄性C57小鼠随机分配至MPTP组和PBS
组，分别腹腔注射20 mg/kg MPTP或等体积无菌PBS，每隔2 h注射一次，共4次。另将36只8周雄性C57小
鼠随机平分为（NC agomir + PBS）组（NCPBS 组）、（NC agomir + MPTP）组（NCMPTP 组）、（miR-218-5p
agomir+PBS）组（218PBS组）、（miR-218-5p agomir+MPTP）组（218MPTP组），每组9只，分别进行双侧黑质立
体定位注射miR-218-5p agomir/NC agomir，3 d后腹腔注射MPTP或PBS。免疫荧光染色和Western blot检测
小鼠黑质多巴胺能神经元酪氨酸羟化酶（TH）的表达；荧光定量 PCR 检测小鼠黑质 miR-218-5p 和 Wnt7a、 Ctnnb1、Lef1、Birc5 mRNA的表达。结果：与PBS组相比，MPTP组小鼠黑质miR-218-5p表达显著下降（P＜ 0.05）；与 NCPBS 组相比，NCMPTP 组 TH+
细胞数量和 TH 蛋白表达减少（P＜0.05），Wnt7a、Ctnnb1、Lef1、 Birc5 mRNA表达下降（P＜0.05）；与NCMPTP组相比，218MPTP组TH+
细胞数量和TH蛋白表达增加（P＜ 0.05），Wnt7a、Ctnnb1、Lef1、Birc5 mRNA 表达上升（P＜0.05）。结论：miR-218-5p 可能通过调控 Wnt/
β-catenin信号通路逆转MPTP诱导的急性PD模型小鼠黑质多巴胺能神经元变性，提示miR-218-5p有可能成
为PD的潜在治疗靶点。 |
| 英文摘要: |
| To investigate the protective effect of miR-218-5p on dopaminergic neurons in the
substantia nigra compacta (SNc) by establishing a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
mouse model of Parkinson’s disease (PD). Methods: A total of 18 8-week-old male C57 mice were randomly
divided into MPTP group and PBS group. Mice were injected intraperitoneally with MPTP (20 mg/kg) or with an
equal amount of PBS every 2 h for a total of 4 doses. An additional 36 8-week-old adult male C57 mice were
randomly divided into 4 groups with 9 mice in each: (NC agomir+PBS) (NCPBS) group, (NC agomir+MPTP)
(NCMPTP) group, (miR-218-5p agomir+PBS) (218PBS) group, and (miR-218-5p agomir+ MPTP) (218MPTP)
group. Bilateral stereotaxic injections of miR-218-5p agomir or NC agomir in the SNc were performed
respectively, then 3 days later, mice were injected intraperitoneally with MPTP or PBS as before. The expression
of tyrosine hydroxylase (TH) protein in the SNc was detected by immunofluorescence and Western blot (WB).
The expression of miR-218-5p, Wnt7a mRNA, Ctnnb1 mRNA, Lef1 mRNA, and Birc5 mRNA in the SNc was
assessed with quantitative real-time PCR (qPCR). Results: Compared with the PBS group, the expression of
miR-218-5p of SNc in the MPTP group decreased obviously (P<0.05). Compared with NCPBS group mice, the
NCMPTP group mice showed a reduced number of TH+ cells, decreased expression of TH protein, and decreased
expression of Wnt7a, Ctnnb1, Lef1, and Birc5 mRNA in the SNc (P<0.05). Compared with NCMPTP group
mice, the 218MPTP group mice had a greater number of TH + cells, increased expression of TH protein, and
increased expression of Wnt7a, Ctnnb1, Lef1, and Birc5 mRNA (P<0.05). Conclusion: MiR-218-5p
significantly alleviates MPTP-induced dopaminergic neuronal degeneration in the SNc, potentially via Wnt/
β-catenin signaling. This finding may provide a potential therapeutic target for the treatment of PD. |
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