依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控

doi:10.13418/j.issn.1001-165x.2024.1.09

中国临床解剖学杂志 ›› 2024, Vol. 42 ›› Issue (1): 47-53.doi: 10.13418/j.issn.1001-165x.2024.1.09

依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控

祁志^#，杨力^#，贾秋叶，陈浩伦，段兆达，吴春云*

昆明医科大学基础医学院人体解剖与组织胚胎学系，昆明 650500

收稿日期:2023-05-05 出版日期:2024-01-25 发布日期:2024-01-30
通讯作者: 吴春云，教授，博士生导师, E-mail：wuchunyunkm@163.com
作者简介:祁志（2000-），男，临床医学本科在读，E-mail：1633690688@qq.com；共同第一作者：杨力（1976-），男，博士研究生，研究方向：神经退变机制，E-mail：yanglikm@163.com
基金资助:
国家自然科学基金（81960223）；云南省科技厅昆明医科大学联合专项（202301AY070001-163）；云南省大学生创新性实验计划项目；昆明医科大学大学生创新性实验计划项目（2022JXD301）

Edaravone regulates Sirt3 expression in lipopolysaccharide-activated microglia via MAPKs signaling pathway

Qi Zhi^#, Yang Li^#, Jia Qiuye, Chen Haolun, Duan Zhaoda, Wu Chunyun*

Department of Human Anatomy and Tissue Embryology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China

Received:2023-05-05 Online:2024-01-25 Published:2024-01-30

摘要/Abstract

摘要： 目的探究依达拉奉对LPS激活的小胶质细胞Sirt3和MAPKs通路相关蛋白的作用及其调控机制。方法采用Western blot和免疫荧光双标染色检测LPS激活的BV2小胶质细胞中Sirt3和MAPKs通路相关蛋白ERK1/2、P38、JNK及p-ERK1/2、p-P38和p-JNK的表达；检测ERK1/2通路抑制剂处理后p-ERK1/2和Sirt3的表达。结果 LPS激活的BV细胞中Sirt3、p-ERK1/2、p-P38和p-JNK表达显著增高，依达拉奉能促进Sirt3和p-ERK1/2过表达，并降低p-P38和p-JNK表达；ERK1/2抑制后p-ERK1/2和Sirt3的蛋白表达降低。依达拉奉可促进激活的BV2细胞中Sirt3和p-ERK1/2过表达，并下调过表达的p-P38和p-JNK。结论依达拉奉可调节BV2细胞中MAPKs信号通路并促进Sirt3生成，可能经ERK/Sirt3通路发挥抗炎作用。

关键词: 依达拉奉； , , Sirt3； , , 小胶质细胞； , , MAPKs信号通路

Abstract: Objective To investigate the effect of edaravone on Sirt3 and MAPKs pathway-related proteins in LPS-activated microglia and its regulatory mechanism. Methods Western Blot and immunofluorescence were used to detect the effect of edaravone on the protein expression of Sirt3 and MAPKs pathway-related proteins ERK1/2, P38, JNK as well as their phosphorylated forms p-ERK1/2, p-P38 and p-JNK in the activated BV2 cells. Western Blot techniques were applied to detect the effects of ERK1/2 pathway inhibitor on the expressions of p-ERK1/2 and Sirt3. Results The expressions of Sirt3, p-ERK1/2, p-P38 and p-JNK in microglia were significantly increased after BV2 cells activation. Edaravone promoted the expression of Sirt3 and p-ERK1/2 and downregulated the expression of p-JNK and p-P38. The protein expression of Sirt3 and p-ERK1/2 decreased after co-treatment with edaravone and ERK1/2 inhibitor. Edaravone promoted the overexpression of Sirt3 and p-ERK1/2 and downregulated the expression of p-JNK and p-P38. Conclusions Edaravone can regulate MAPKs signaling pathway and promote Sirt3 production in BV2 cells, possibly regulates neuroinflammatory responses via ERK/Sirt3 signaling pathway.

Key words: Edaravone; , , Sirt3; , , Microglia; , , MAPKs signaling pathway

中图分类号:

R363.21

祁志, 杨力, 贾秋叶, 陈浩伦, 段兆达, 吴春云. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控[J]. 中国临床解剖学杂志, 2024, 42(1): 47-53.

Qi Zhi, Yang Li, Jia Qiuye, Chen Haolun, Duan Zhaoda, Wu Chunyun. Edaravone regulates Sirt3 expression in lipopolysaccharide-activated microglia via MAPKs signaling pathway[J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 47-53.

参考文献 14

[1]	Spiteri AG, Wishart CL, Pamphlett R, et al. Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function[J]. Acta Neuropathol, 2022, 143(2): 179-224. DOI: 10.1007/s00401-021-02384-2.
[2]	Wolf SA, Boddeke HW, Kettenmann H. Microglia in physiology and disease[J]. Annu Rev Physiol, 2017, 79: 619-643. DOI: 10.1146/ annurev-physiol-022516-034406.
[3]	Yuan Y, Zha H, Rangarajan P, et al. Anti-inflammatory effects of edaravone and scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV2 microglia[J]. BMC Neurosci, 2014, 15: 125. DOI: 10.1186/s12868-014-0125-3.
[4]	Chen HL, Jia WJ, Li HE, et al. Scutellarin exerts anti-inflammatory effects in activated microglia/brain macrophage in cerebral ischemia and in activated BV2 microglia through regulation of MAPKs signaling pathway[J]. Neuromolecular Med, 2020, 22(2): 264-277. DOI: 10.1007/s12017-019-08582-2.
[5]	Sun J, Pu C, Yang E, et al. Macrophage/Microglia Sirt3 contributes to the anti-inflammatory effects of resveratrol against experimental intracerebral hemorrhage in mice[J]. Cell Mol Neurobiol, 2023, 43(6): 2871-2882. DOI: 10.1007/s10571-023-01325-9.
[6]	虞舒蓓, 林淑. 依达拉奉对脂多糖激活的BV2小胶质细胞中促炎细胞因子的影响[J]. 中国临床药理学杂志, 2019, 35(12): 1244-1246. DOI: 10.13699/j.cnki.1001-6821.2019.12.006.
[7]	Yuan Y, Wu C, Ling EA. Heterogeneity of microglia phenotypes: developmental, functional and some therapeutic considerations[J]. Curr Pharm Des, 2019, 25(21): 2375-2393. DOI: 10.2174/138161282566619 0722114248.
[8]	Yang L, Zhou R, Tong Y, et al. Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation[J]. Neurobiol Dis, 2020, 140: 104814. DOI: 10.1016/j.nbd.2020.104814.
[9]	Plastira I, Bernhart E, Joshi L, et al. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia[J]. J Neuroinflammation, 2020, 17(1): 127. DOI: 10.1186/s12974-020-01809-1.
[10]	Meng W, Wang X, Lu L, et al. Effects of edaravone on cerebral ischemia-reperfusion in mice through the TLR4/NF-κB/TNF-α pathway[J]. Panminerva Med, 2021, 63(3): 383-384. DOI: 10.23736/S0031-0808.19.03693-0.
[11]	Liu SJ, Liu XY, Li JH, et al. Gastrodin attenuates microglia activation through renin-angiotensin system and Sirtuin3 pathway[J]. Neurochem Int, 2018, 120: 49-63. DOI: 10.1016/j.neuint.2018.07.012.
[12]	Yin J, Han P, Tang Z, et al. Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke[J]. J Cereb Blood Flow Metab, 2015, 35(11): 1783-1789. DOI: 10.1038/jcbfm.2015.123.
[13]	Ding M, Tolbert E, Birkenbach M, et al. Treprostinil reduces mitochondrial injury during rat renal ischemia-reperfusion injury[J]. Biomed Pharmacother, 2021, 141: 111912. DOI: 10.1016/j.biopha.2021.111912.
[14]	Li N, Li X, Zheng K, et al. Inhibition of Sirtuin 3 prevents titanium particle-induced bone resorption and osteoclastsogenesis via suppressing ERK and JNK signaling[J]. Int J Biol Sci, 2021, 17(5): 1382-1394. DOI: 10.7150 /ijbs.53992.

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依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控

Edaravone regulates Sirt3 expression in lipopolysaccharide-activated microglia via MAPKs signaling pathway

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