天麻素通过SOX2/β-catenin通路抑制脂多糖诱导的小胶质细胞活化  

Gastrodin inhibits the lipopolysaccharide-induced microglia activation through the SOX2/β-catenin signaling pathway

作　　者：张幸霖 石金沙 付宏铭 黄俣瑞 石浩龙 左涵珺 郭涛 李娟娟 ZHANG Xinglin;SHI Jinsha;Fu Hongming;HUANG Yurui;SHI Haolong;ZUO Hanjun;GUO Tao;LI Juanjuan(Department of Human Anatomy and Histology&Embryology,Faculty of Basic Medical Sciences,Kunming Medical University,Kunming 650500,China)

机构地区：[1]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

出　　处：《神经解剖学杂志》2024年第3期365-372,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31960194);云南省大学生创新性实验计划项目(2022JXD273)。

摘　　要：目的:研究天麻素(GAS)对脂多糖(LPS)激活的BV2小胶质细胞性别决定区Y框蛋白2(SOX2)/β-连环蛋白(β-catenin)通路表达的影响。方法:体外培养BV2小胶质细胞,分为对照组(Control)、LPS刺激组(LPS)、LPS+0.17 mmol/L GAS处理组(LPS+GAS-L)、LPS+0.34 mmol/L GAS处理组(LPS+GAS-H)、SOX2抑制剂丙萘洛尔(PR)处理组(PR)、LPS+PR处理组(LPS+PR)、LPS+PR+GAS处理组(LPS+PR+GAS)。通过CCK-8检测PR对BV2小胶质细胞活力的影响,并通过Western Blot和免疫荧光双标染色检测SOX2、β-catenin、甘露糖受体(CD206)和肿瘤坏死因子-α(TNF-α)的表达变化。结果:PR在0~40μmol/L范围内不会引起显著的BV2小胶质细胞死亡;LPS刺激组中SOX2、β-catenin和TNF-α蛋白表达明显增强,而CD206表达显著降低(P<0.05)。GAS干预后SOX2、β-catenin和TNF-α表达显著减少,而CD206明显升高(P<0.05);与LPS组相比,用PR阻断SOX2后β-catenin和TNF-α蛋白表达显著降低(P<0.05),而PR与GAS联合应用与单纯GAS干预组相比,β-catenin和TNF-α蛋白表达无明显差异。结论:天麻素可能通过抑制SOX2/β-catenin通路减轻小胶质细胞的激活,发挥抗炎作用。Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalol group(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0~40μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-αsignificantly increased in the LPS group,while CD206 decreased(P<0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-αsignificantly decreased,while CD206 increased(P<0.05).Compared to the LPS group,the expression levels ofβ-catenin and TNF-αsignificantly decreased in the PR group(P<0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibition of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

关 键 词：天麻素 脂多糖 性别决定区Y框蛋白2 Β-连环蛋白 小胶质细胞 

分 类 号：R285[医药卫生—中药学]