安徽医科大学学报2025，Vol.60Issue(11)：2011-2018,8.DOI:10.19405/j.cnki.issn1000-1492.2025.11.004
IQGAP1在氧糖剥夺/复氧诱导的小胶质细胞极化中的作用及其机制
The role and mechanism of IQGAP1 in oxygen-glucose deprivation/reoxygenation induced microglial polarization
摘要
Abstract
Objective To investigate the role and mechanism of IQ motif containing GTPase activating protein 1(IQGAP1)in oxygen-glucose deprivation/reoxygenation(OGD/R)-induced polarization of BV-2 microglia cells.Methods The IQGAP1 overexpression plasmid(oe-IQGAP1)and its negative control plasmid(Vector)were transfected into BV-2 cells,and then the polarization of BV-2 cells was induced by OGD/R,and exogenous inter-feron-γ(IFN-γ)recombinant protein was used for intervention.Cell proliferation rate was detected by cell counting kit-8(CCK-8)assay.The level of lactate dehydrogenase(LDH)in the supernatant was detected using a test kit.The mRNA expression levels of IQGAP1,IFN-γ and microglial polarization markers inducible nitric oxide synthase(iNOS),CD86,CD206 and arginase1(Arg1)were detected by quantitative real-time polymerase chain reaction(RT-qPCR).The levels of IFN-γ,tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4 and IL-10 in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of IQGAP1 and IFN-γ were detected by Western blot.Results Following OGD/R treatment,the proliferation rate of BV-2 cells,the levels of IL-4 and IL-10 in the supernatant,and the mRNA expression levels of CD206 and Arg1 were significantly reduced(all P＜0.05).In contrast,the levels of LDH,TNF-α and IL-1 β in the supernatant,as well as the mRNA expression levels of iNOS and CD86 in the cells significantly increased(all P＜0.05).More-over,both the mRNA and protein expression levels of IQGAP1 in the cells significantly decreased(P＜0.05).Following IQGAP1 overexpression,the levels of IL-4 and IL-10 in the supernatant of BV-2 cells,along with the mRNA expression levels of CD206 and Arg1 in the cells,were significantly elevated under OGD/R conditions(all P＜0.05).Meanwhile,the levels of TNF-α and IL-1 β in the supernatant and the mRNA expression levels of iNOS and CD86 in the cells significantly decreased(all P＜0.05).Additionally,both the intracellular expression and secretion of IFN-γ protein were reduced(all P＜0.05),whereas the mRNA expression of IFN-γ remained un-changed.However,combined intervention with exogenous IFN-γ recombinant protein obviously reversed the inhibi-tory effect of IQGAP1 overexpression on OGD/R-induced M1 polarization of microglia.Conclusion IQGAP1 over-expression inhibits M1 polarization of microglia under OGD/R conditions through the suppression of IFN-γ expres-sion and secretion.关键词
小胶质细胞/M1型极化/氧糖剥夺/复氧/含IQ基元GTP酶激活蛋白1/干扰素-γKey words
microglia/M1 polarization/oxygen-glucose deprivation/reoxygenation/IQ motif containing GTPase activating protein 1/interferon-γ分类
医药卫生引用本文复制引用
朝博,任君浩,郭若宇,苏优勒,马英..IQGAP1在氧糖剥夺/复氧诱导的小胶质细胞极化中的作用及其机制[J].安徽医科大学学报,2025,60(11):2011-2018,8.基金项目
内蒙古自治区自然科学基金(编号:2023LHMS08029) （编号:2023LHMS08029）
内蒙古自治区首府地区公立医院高水平临床专科建设科技项目(编号:2024SGGZ083) Natural Science Foundation of Inner Mongolia Autonomous Region(No.2023LHMS08029) （编号:2024SGGZ083）
High-Level Clinical Specialty Construction Science and Technology Project for Public Hospitals in Capital Region of Inner Mongolia Autonomous Region(No.2024SGGZ083) （No.2024SGGZ083）
