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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (5): 1-7.doi: 10.6040/j.issn.1671-7554.0.2022.0102

• 基础医学 •    下一篇

生长分化因子15在LPS诱导的帕金森病模型中的保护作用及机制

张秀芳,李沛铮,张博涵,孙丛丛,刘艺鸣   

  1. 山东大学齐鲁医院神经内科, 山东 济南 250012
  • 发布日期:2022-06-01
  • 通讯作者: 刘艺鸣. E-mail:liuym@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(82171245)

Protective effect and mechanism of growth differentiation factor-15 in LPS-induced models of Parkinsons disease

ZHANG Xiufang, LI Peizheng, ZHANG Bohan, SUN Congcong, LIU Yiming   

  1. Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-06-01

摘要: 目的 探究生长分化因子15(GDF15)在脂多糖(LPS)诱导的帕金森病神经炎症中的保护作用及其机制。 方法 筛选LPS作用于BV2细胞的合适时间,分为空白组、3 h组、6 h组、12 h组和24 h组;筛选LPS作用于BV2细胞的合适浓度,分为空白组、0.5 mg/mL组、1 mg/mL组和2 mg/mL组;探究外源性GDF15作用时,BV2细胞分为空白组、LPS组和LPS+GDF15组;实验动物分为野生小鼠对照组(WT组)、野生小鼠模型组(WT+LPS组)和GDF15敲除小鼠模型组(KO+LPS组)。采用Western blotting法检测信号转导和转录激活因子3(STAT3)/核转录因子κB(NF-κB)/细胞外信号调节激酶(ERK)蛋白表达水平,采用qPCR法检测肿瘤坏死因子(TNF-α)、白细胞介素(IL-1β)、诱导型一氧化氮合酶(iNOS)、环氧合酶-2(COX-2)的表达水平,使用显微镜观察BV2小胶质细胞形态变化。 结果 外源性GDF15通过抑制STAT3/NF-κB/ERK信号通路,可降低TNF-α、IL-1β、iNOS、COX-2等炎症分子的表达,GDF15敲除小鼠模型组黑质、纹状体的炎症反应增强,TNF-α、IL-1β、iNOS、COX-2等炎症分子的表达升高。 结论 GDF15在帕金森病的炎症模型中可以通过STAT3/NF-κB/ERK信号通路降低炎症因子的表达,GDF15通过抑制炎症因子的分泌进而在帕金森病的进展中发挥保护作用,为帕金森病的防治提供新的靶点。

关键词: 生长分化因子15, 帕金森病, 神经炎症, 信号通路, 小鼠

Abstract: Objective To investigate the protective effect and mechanism of growth differentiation factor 15(GDF15)in lipopolysaccharide(LPS)induced neuroinflammation associated with Parkinsons disease. Methods To explore the optimum time of LPS, BV2 cells were divided into blank, 3 h, 6 h, 12 h and 24 h groups; to explore the optimum concentration of LPS, BV2 cells were divided into blank, 0.5, 1 and 2mg/mL groups; to explore the effect of GDF15, BV2 cells were divided into blank, LPS and LPS+GDF15 groups. The mice were divided into WT, WT+LPS and KO-LPS group. The protein expressions of STAT3, NF-κB and ERK were detected with Western blotting. The mRNA expressions of TNF-α, IL-1β, iNOS and COX-2 were detected with qPCR. The effect of GDF15 on the morphology of LPS-induced BV2 cells was observed with a microscope. Results GDF-15 suppressed the expressions of TNF-α, IL-1β, iNOS and COX-2 by inhibiting the STAT3/NF-κB/ERK signaling pathway. In the substantia nigra and striatum of the GDF15 knockout mice, the expressions of TNF-α, IL-1β, iNOS and COX-2 increased. Conclusion GDF15 can attenuate the expressions of TNF-α, IL-1β, iNOS and COX-2 through STAT3/NF-κB/ERK signaling pathway, indicating it is a protective factor in the progression of Parkinsons disease. It can provide a new therapeutic target for the prevention and treatment of this disease.

Key words: Growth differentiation factor 15, Parkinsons disease, Neuroinflammation, Signal pathway, Mice

中图分类号: 

  • R574
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