miR-let-7f减轻小胶质细胞氧糖剥夺诱导的炎症反应及其机制OA

Objective This study aims to investigate the regulatory effect of miR-let-7f on oxygen-glucose deprivation-induced inflammatory responses in microglia and its underlying molecular mechanism.Methods The murine microglial cell line BV2 was cultured to establish an oxygen-glucose deprivation/reoxygenation(OGD/R)cell model.miR-let-7f mimics and inhibitors were designed and synthesized.Quantitative real-time PCR(qPCR)and enzyme-linked immunosorbent assay(ELISA)were employed to quantify the expression levels of miR-let-7f,high mobility group AT-hook 2(HMGA2),and inflammatory cytokines across all treatment groups.Cellular immu‑nofluorescence staining was conducted to visualize the subcellular localization and activation status of microglia.Results Transfection with miR-let-7f mimics and inhibitor significantly upregulated and downregulated miR-let-7f expression in BV2 cells,respectively(P<0.000 1).OGD/R treatment increased the expression of the pro-inflammatory protein HMGA2 and the inflammatory cytokines tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)(P<0.05),accompanied by increased nuclear translocation of NF-κB p65.Treatment with miR-let-7f mimics significantly reduced HMGA2 and inflammatory cytokine levels(P<0.05)and decreased NF-κB p65 nuclear translocation.Following the addition of the miR-let-7f inhibitor,these inhibitory effects were signifi‑cantly attenuated(P<0.05).Conclusions miR-let-7f exerts anti-inflammatory effects in BV2 microglia under OGD/R conditions.This bioactivity may be mediated via the regulation of HMGA2 expression and subsequent sup‑pression of the NF-κB signaling pathway.The present study provides robust experimental evidence for the interven‑tion of neuroinflammation secondary to cerebral ischemia and hypoxia.