白藜芦醇通过下调YTHDF1表达抑制巨噬细胞M1极  

Resveratrol inhibits macrophage M1 polarization by down-regulating YTHDF1 expression

作　　者：皮慧 王玉 汪光亮 赵国军 高军 PI Hui;WANG Yu;WANG Guangliang;ZHAO Guojun;GAO Jun(Faculty of Basic Medical Sciences,Dali University,Dali 671013,China;Affiliated Qingyuan Hospital,Guangzhou Medical University(Qingyuan People′s Hospital),Qingyuan 511518,China;Faculty of Basic Medical Sciences,Guilin Medical University,Guilin 541199,China)

机构地区：[1]大理大学基础医学院,大理671013 [2]广州医科大学附属清远医院(清远市人民医院),清远511518 [3]桂林医学院基础医学院,桂林541199

出　　处：《华夏医学》2025年第2期3-11,共9页Acta Medicinae Sinica

基　　金：国家自然科学基金(81870337);广东省自然科学基金面上项目(2024A1515012850)。

摘　　要：目的探究白藜芦醇(RES)对巨噬细胞M1极化的作用及机制。方法采用MTT检测RES以不同浓度和时间梯度处理对THP-1巨噬细胞活性的影响;采用qRT-PCR检测RES对巨噬细胞M1极化标志物肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)表达以及m6A修饰相关酶METTL3、METTL14、WTAP、YTHDC1、YTHDC2、YTHDF1、YTHDF2、FTO、ALKBH5、HNRNPC、RBM15和VIRMA表达的影响;分别构建对照(NC)和YTHDF1小干扰RNA(siRNA);通过YTHDF1 siRNA转染处理细胞,利用qRT-PCR与Western blot分别检测YTHDF1以及TNF-α、IL-6和IL-1β的mRNA和蛋白表达水平。结果RES处理后,TNF-α、IL-6和IL-1β的mRNA水平显著降低,m6A修饰相关酶YTHDF1表达下降,以上差异均有统计学意义(P<0.05);敲低YTHDF1后,TNF-α、IL-6和IL-1β的mRNA和蛋白表达均下调,采用RES处理后,仅IL-1β蛋白表达显著降低(P<0.05)。结论RES能够抑制巨噬细胞M1极化,其机制可能与调控YTHDF1的表达有关。Objective To investigate the effect and mechanism of resveratrol(RES)on M1 polarization in macrophages.Methods The effect of treatment of RES at different concentrations and time gradients on THP-1 macrophages activity was detected by MTT assay.The effect of RES on the expression of the macrophage M1 polarization markers tumor necrosis factor-α(TNF-α),Interleukin-6(IL-6)and Interleukin-1β(IL-1β),as well as the expression of the m6 A modification-related enzymes METTL3,METTL14,WTAP,YTHDC1,YTHDC2,YTHDF1,YTHDF2,FTO,ALKBH5,HNRNPC,RBM15,and VIRMA was detected by qRT-PCR.Control(NC)and YTHDF1 small interfering RNA(siRNA)were constructed respectively.Cells were treated by YTHDF1 siRNA transfection,and the mRNA and protein expression levels of YTHDF1 as well as TNF-α,IL-6 and IL-1βwere detected by qRT-PCR and Western blot,respectively.Results After RES treatment,the mRNA levels of TNF-α,IL-6 and IL-1βwere significantly reduced,and the expression of m6 A modification-related enzyme YTHDF1 was decreased,and the differences were all statistically significant(P<0.05).Knockdown of YTHDF1 resulted in downregulation of mRNA and protein expression of TNF-α,IL-6 and IL-1β.After further RES treatment,only the expression of IL-1βprotein was significantly reduced.Conclusion RES can inhibit macrophage M1 polarization by a mechanism that may be related to the regulation of YTHDF1 expression.

关 键 词：白藜芦醇 YTHDF1 巨噬细胞极化 

分 类 号：R541.4[医药卫生—心血管疾病]