硫化氢通过JAK2/STAT3通路抑制脂多糖诱导的小胶质细胞M1型极化Hydrogen sulfide inhibits the M1 polarization of microglia induced by lipopolysaccharide through the JAK/STAT3 pathway
刘剑锋;陈杉杉;冯伟;周寿红;
摘要(Abstract):
目的观察硫化氢(H_2S)对脂多糖(LPS)诱导的小胶质细胞极化的影响并探讨JAK2/STAT3信号通路是否介导其作用。方法将培养的N9小胶质细胞随机分为对照组、LPS组、硫氢化钠(NaHS)组、LPS+NaHS组、蛋白酪氨酸激酶(JAK2)/信号转导和转录激活因子(STAT3)抑制剂α-氰基-(3,4-羟基)N-苄苯乙烯胺(AG-490)组、LPS+NaHS+AG-490组共6组,每组设3个复孔。采用MTT法检测各组细胞活力,采用ELISA法检测各组胶质细胞及培养上清液中白细胞介素1β(IL-1β)、IL-6、IL-4 IL-10水平,采用Western-blot检测各组细胞精氨酸酶1(Arg1)、诱导型一氧化氮合酶(iNOS)、磷酸化JAK2(p-JAK2)和磷酸化STAT3(p-STAT3)蛋白表达。结果与对照组比较,LPS组细胞Arg1蛋白及IL-4和IL-10表达水平增加,而iNOS蛋白、IL-1β、IL-6、p-JAK2蛋白和p-STAT3蛋白表达降低,p-JAK2/t-JAK和p-STAT3/t-STAT3比值降低(均P<0.05)。与LPS组比较,LPS+NaHS组细胞Arg1蛋白及IL-4和IL-10表达水平增加,而iNOS蛋白、IL-1β、IL-6、p-JAK2蛋白和p-STAT3蛋白表达降低,p-JAK2/t-JAK2和p-STAT3/t-STAT3比值降低(均P<0.05)。JAK2/STAT3信号通路抑制剂AG-490可减弱NaHS的作用。结论 H_2S可抑制LPS诱导的小胶质细胞M1型极化,其机制可能是通过JAK2/STAT3信号通路实现。
关键词(KeyWords): 硫化氢;脂多糖;小神经胶质细胞;极化;JAK2/STAT3信号通路
基金项目(Foundation): 湖南省卫生健康委科研计划课题项目(C2019097);; 湖南省自然科学基金资助项目(No 2016JJ2110);; 广西脑与认知神经科学重点实验室开放课题(GKLBCN-20190105-02)
作者(Author): 刘剑锋;陈杉杉;冯伟;周寿红;
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DOI:
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