实用医学杂志2024，Vol.40Issue(14)：1915-1921,7.DOI:10.3969/j.issn.1006-5725.2024.14.003
小檗碱联合姜黄素调控M1巨噬细胞极化对动脉粥样硬化的作用机制
Effect of M1 macrophage polarization regulated by berberine combined with curcumin on atherosclerosis
摘要
Abstract
Objective To explore the effect and mechanism of berberine combined with curcumin on ath-erosclerosis(AS)by mediating M1 macrophages polarization.Methods M1-type macrophages were obtained from mouse mononuclear macrophages(RAW264.7)induced by lipopolysaccharide(LPS,100 ng/mL)and interferon(IFN)-γ(20 ng/mL).A cell model was established.The cells were divided into a control group,model group,berberine group,curcumin group and berberine plus curcumin group.Concentrations of berberine and curcumin were detected by CCK-8 assay.The expression levels of M1-type macrophage markers iNOS,TNF-α,CXCL9 and p-STAT6/STAT6 in macrophage supernatant were detected by ELISA.Levels of iNOS,TNF-α and CXCL9 mRNA were detected by RT-PCR.Levels of iNOS,STAT6 and p-STAT6 proteins in each group were detected by Western blot.After down-regulation of STAT6 level by siRNA technology,expression of p-STAT6 protein was detected by Western blot.Expression levels of iNOS,TNF-α,CXCL9 and p-STAT6 were detected by ELISA.Results In the polarization of M1 macrophages induced by LPS and IFN-γ,berberine(25 μmol/L)and curcumin(20 μmol/L)were the best concentrations as compared with other drug concentration groups,and neither alone nor combined use could significantly inhibit the viability of RAW264.7 cells(P<0.05).As compared with the normal group,iNOS,TNF-α and CXCL9 mRNA and protein levels were increased in the model group,while P-STAT6/STAT6 levels were decreased,with statistical differences(P<0.05).As compared with the model group,iNOS,TNF-α and CXCL9 mRNA and protein levels in the berberine group,curcumin group,and berberine plus curcumin group were decreased,while P-STAT6/STAT6 levels were increased,and the changes were more obvious in berberine plus curcumin group,with statistical difference(P<0.05).After transfection of STAT6 siRNA in M1 macrophages in the berberine plus curcumin group,P-STAT6 levels were down-regulated,while expressions of iNOS,TNF-α and CXCL9 were up-regulated,with statistical differences(P<0.05).Conclusions Both berberine and curcumin can inhibit the activity of M1-type macrophages and reduce inflammatory response.The action of berberine combined with curcumin is more advantageous than that of either drug alone,which may be the main mechanism of action through activation of STAT6.关键词
动脉粥样硬化/M1型巨噬细胞/小檗碱/姜黄素/STAT6Key words
atherosclerosis/M1 macrophage/berberine/curcumin/STAT6分类
医药卫生引用本文复制引用
陈玉善,王婷婷,韩心怡,华成俊,靳博远,尚莎莎,宗永华,梁亚州..小檗碱联合姜黄素调控M1巨噬细胞极化对动脉粥样硬化的作用机制[J].实用医学杂志,2024,40(14):1915-1921,7.基金项目
国家重点研发计划(编号:2020YFC2004706) （编号:2020YFC2004706）
国家自然科学基金项目(编号:82004311) （编号:82004311）
河南省中医管理局中医药科学研究专项课题(编号:2018JDZX107,2022JDZX026,2019JDZX2044) （编号:2018JDZX107,2022JDZX026,2019JDZX2044）
