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目的 观察辛伐他汀对炎症型M1型巨噬细胞极性的影响,探讨他汀类药物在细胞水平的抗炎作用.方法 以γ-干扰素及脂多糖刺激小鼠骨髓来源巨噬细胞诱导成M1型炎症性巨噬细胞模型,给予辛伐他汀1.0、2.5、5.0 μmol/L分别干预9h,以流式细胞仪检测巨噬细胞膜CD16/23、CD206标志分子的表达,用ELISA检测白细胞介素(IL)-10和IL-12的分泌.结果 γ-干扰素及脂多糖刺激的巨噬细胞CD16/32表达阳性率为86.39％±2.24％,IL-12分泌量为(1562±217) pg/ml,符合M1型巨噬细胞表型特点；与辛伐他汀1.0、2.5、5.0 μmol/L孵育9h后测定的CD206表达阳性率分别为68.10％±2.48％、75.28％±1.66％、86.32％±2.19％,IL-10浓度分别为(500±5)、(675±28)、(916±15) pg/ml,均高于M1型巨噬细胞[9.67％±5.48％、(298±11) pg/ml,均P＜0.01],且与M2型巨噬细胞的表型特点类似.结论 辛伐他汀可通过诱导炎症型M1型巨噬细胞转化为抗炎型的M2型巨噬细胞而发挥抗炎作用.

Objective To explore the effects of statin on pro-inflammatory macrophage phenotype in a murine M1 macrophage model.Methods Macrophages isolated from murine bone barrow were stimulated with interferon-gamma (IFN-γ) and lipopolysaccharide (LPS) to establish a M1 macrophage model.And 1.0,2.5,5.0 μmol/L of simvastatin were added to M1 macrophages for a 9-hour culture.Cell surface markers CD16/23 and CD206 were detected by fluorescence activated cell sorter (FACS) and interleukin-10 (IL-10) and IL-12 by ELISA.Results The CD16/32 expression was 86.39％ ± 2.24％ and IL-12secretion (1562 ± 217) pg/ml in IFN-γ and LPS-stimulated macrophages.After a 9-hour incubation with 1.0,2.5,5.0 μmol/L simvastatin,the CD206 expression levels were 68.10％ ± 2.48％,75.28％ ± 1.66％,86.32％ ±2.19％ and the secretion of IL-10 (500 ±5),(675 ±28) and (916 ± 15) pg/ml respectively.By analysis of variance and q test of mean,the difference was statistically significant (all P ＜0.01) between the groups of M1 model(9.67％ ±5.48％,(298 ± 11) pg/ml).And the phenotypic features were similar to those of the groups of M2 model.Conclusion Simvastatin may inhibit inflammation by enhancing the switching of M1 macrophage to M2 macrophage phenotype.