七氟醚通过p38/MAPK信号通路抑制脂多糖诱导的肺泡巨噬细胞M1型极化

Sevoflurane inhibits M1-type polarization of alveolar macrophages induced by lipopolysaccharide through p38/MAPK signaling pathway

目的:探讨七氟醚通过调控p38/MAPK信号通路对脂多糖(LPS)诱导的肺泡巨噬细胞M1型极化的影响。方法:采用1μg/ml的LPS刺激RAW264.7细胞24 h,暴露于不同浓度(1%、2%、4%)七氟醚后,分别采用MTT、ELISA、RT-qPCR及Western blot检测细胞活力、炎症相关因子及相关通路蛋白的表达情况。结果:LPS刺激使RAW264.7细胞活力降低,M1型促炎症因子的表达升高,M2型抗炎症因子的表达降低,p38/MAPK磷酸化蛋白的表达水平升高(P<0.05)。七氟醚处理后,细胞活力明显增强,抗炎因子水平明显上升,促炎因子水平显著下降,p38蛋白的磷酸化水平降低,且与七氟醚浓度具有依赖性(P<0.05)。p38/MAPK抑制剂SB202190加剧了七氟醚对肺泡巨噬细胞M1型极化的抑制作用。结论:七氟醚能够抑制LPS诱导的肺泡巨噬细胞M1型极化,可能是通过调节p38/MAPK信号通路实现的。

Objective:To investigate the effect of sevoflurane on M1 polarization of alveolar macrophages induced by lipopolysaccharide(LPS)by regulating p38/MAPK signaling pathway.Methods:RAW264.7 cells were stimulated with 1μg/ml LPS for 24 h and exposed to different concentrations(1%,2%,4%)of sevoflurane.After that,MTT,ELISA,RT-qPCR and Western blot assays were used to detect cell viability,inflammation factors and signaling pathway-related protein levels.Results:LPS stimulation led to decreased cell viability and M2-type anti-inflammatory cytokine levels,and increased M1-type pro-inflammatory cytokine levels and phosphorylation of p38/MAPK in RAW264.7 cells(P<0.05).After sevoflurane treatment,the cell viability and anti-inflammatory cytokine levels were significantly enhanced,and the pro-inflammatory cytokine levels and phosphorylation of p38 were significantly decreased in a concentration-dependent manner(P<0.05).The p38/MAPK inhibitor SB202190 intensified the inhibitory effect of sevoflurane on M1-type polarization of alveolar macrophages.Conclusion:Sevoflurane inhibits LPS-induced M1 polarization of alveolar macrophages,possibly by regulation of the p38/MAPK signaling pathway.