芝麻酚通过AMPK信号通路调控巨噬细胞极化减轻脂肪组织炎症

Sesamol reduces adipose tissue inflammation by regulating macrophage polarization through AMPK signaling pathway

目的探讨芝麻酚(sesamol,SEM)对高脂饮食诱导的肥胖小鼠脂肪组织炎症的影响及对脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7巨噬细胞极化的调控分子机制。方法将C57BL/6J小鼠随机分成正常对照组、肥胖模型对照组和SEM干预组。干预结束后取小鼠血清和脂肪组织,ELISA法测定小鼠血清和脂肪组织中炎症因子、抗炎因子及趋化因子的分泌水平,Western blot法测定脂肪组织巨噬细胞M1型极化标志物的蛋白表达水平。以LPS刺激RAW264.7巨噬细胞诱导炎症模型并用SEM进行干预,使用AMPK抑制剂compound C进行机制探讨和验证,Western blot法检测巨噬细胞极化标志物及AMPK信号通路相关蛋白表达水平,ELISA法检测巨噬细胞炎症相关因子。结果体内实验发现,SEM可降低肥胖小鼠血清和脂肪组织中IL-6、TNF-α和MCP-1分泌水平,提高IL-10分泌水平,减少M1型巨噬细胞标志物CD11c蛋白表达。体外实验发现,SEM能够激活巨噬细胞AMPK,上调PGC-1α、下调NF-κB表达,降低CD11c、IL-6、TNF-α,升高CD206、IL-10水平,而compound C可以减弱SEM的上述作用。结论SEM可通过激活AMPK信号通路调控巨噬细胞极化减轻脂肪组织炎症。

Aim To investigate the effects of sesamol(SEM)on adipose tissue inflammation induced by high fat diet in obese mice and the regulatory mechanism of RAW264.7 macrophage polarization induced by lipopolysaccharide.Methods C57BL/6J mice were randomly divided into normal control group,obesity model control group and sesamol intervention group.ELISA was used to investigate the expression levels of inflammatory factors,anti-inflammatory factor and chemokine in serum and adipose tissue.Western blot was used to investigate the protein expression level of M1 macrophage polarization marker in adipose tissue.RAW264.7 macrophages were cultured with lipopolysaccharide and were treated with sesamol,with or without AMPK inhibitor compound C.Western blot was utilized to detect the expression levels of macrophage polarization markers and AMPK signaling pathway related proteins,and ELISA was utilized to detect macrophage inflammatory cytokine.Results In vivo experiment showed that sesamol could reduce the secretion levels of interleukin-6,tumor necrosis factor-αand monocyte chemokine in serum and adipose tissue,increase the secretion level of interleukin-10,and reduce the expression of CD11c protein.In vitro experiment,sesamol activated AMPK,and subsequently up-regulated PGC-1αand down-regulated NF-κB.Also,the sesamol decreased the CD11c,IL-6 and TNF-α,and increased the CD206 and IL-10.The AMPK specific inhibitor compound C could reduce all these effects of sesamol.Conclusions Sesamol modulates macrophage polarization and alleviates subsequent adipose inflammation by activating the AMPK signaling pathway.