FGF21对Aβ<sub>25-35</sub>导致星形胶质细胞损伤的保护作用及机制研究

孙岩; 高向东; 陈松

doi:10.11665/j.issn.1000-5048.20190415

FGF21对Aβ_25-35导致星形胶质细胞损伤的保护作用及机制研究

中国药科大学生命科学与技术学院江苏省生物药物成药性研究重点实验室

基金项目: 国家自然科学基金资助项目(No.81673435,No.81872850)

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出版历程
- 刊出日期: 2019-08-24

Effect and mechanism of FGF21 on astrocyte damage induced by Aβ_25-35

摘要

摘要: 以Aβ_25-35诱导星形胶质细胞建立损伤模型，探讨阿尔茨海默病(Alzheimer′s disease，AD)样病变中成纤维细胞生长因子21(fibroblast growth factor 21，FGF21)对星形胶质细胞的作用及机制。采用Aβ_25-35诱导C6星形胶质细胞株及原代星形胶质细胞损伤建立细胞模型；以不同浓度的FGF21对Aβ_25-35诱导细胞损伤模型干预，MTT法检测细胞活性；采用DCFH-DA探针结合流式细胞仪检测FGF21及Aβ_25-35对C6细胞内活性氧(reactive oxygen species，ROS)水平的作用；Western blot检测FGF21及Aβ_25-35对C6细胞中丝裂原活化蛋白激酶(mitogen-activated protein kinases，MAPKs)活性的影响。结果显示:FGF21能够减少Aβ_25-35导致C6细胞及原代星形胶质细胞的损伤，下调C6细胞内异常ROS水平，同时缓解Aβ_25-35引起的C6细胞MEK1/2、ERK1/2、p38磷酸化水平的异常，提示FGF21可能通过调控ROS途径及MAPKs信号通路进而缓解Aβ_25-35导致的星形胶质细胞损伤。
- 成纤维细胞生长因子21 /
- 阿尔茨海默病 /
- 星形胶质细胞 /
- 活性氧 /
- 丝裂原活化蛋白激酶
Abstract: To investigate the effects and mechanism of fibroblast growth factor 21(FGF21)on astrocytes in AD-like lesions, Aβ_25-35 was used to induce astrocyte model damaged. Cell model was established by inducing C6 astrocyte cell line and primary astrocyte damage with Aβ_25-35_.Different concentrations of FGF21 were used to intervene cell injury model induced by Aβ_25-35, and cell viabilities were detected by MTT assay. Effects of FGF21 and Aβ_25-35 on reactive oxygen species(ROS)levels in C6 cells were tested using DCFH-DA probe and flow cytometry. Western blot was used to assess the effects of FGF21 and Aβ_25-35 on the activities of mitogen-activated protein kinases(MAPKs)in C6 cells. The results showed that FGF21 could reduce the damage of C6 cells and primary astrocytes induced by Aβ_25-35, down-regulate the abnormal ROS level in C6 cells, and alleviate the abnormal phosphorylation levels of MEK1/2, ERK1/2 and p38 in C6 cells induced by Aβ_25-35, suggesting that FGF21 may attenuate Aβ_25-35-induced astrocyte damage by regulating ROS pathway and MAPKs signaling pathway.
- fibroblast growth factor 21 /
- Alzheimer′s disease /
- astrocytes /
- reactive oxygen species /
- mitogen-activated protein kinases

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