湖南中医药大学学报2026，Vol.46Issue(5)：889-897,9.DOI:10.3969/j.issn.1674-070X.2026.05.003
小檗碱通过SPHK2/S1P/ERK5通路对ox-LDL诱导的巨噬细胞胞葬功能障碍的影响
Effects of berberine on low-density lipoprotein(ox-LDL)-induced efferocytosis dysfunction in macrophages via the SPHK2/S1P/ERK5 pathway
摘要
Abstract
Objective To investigate the effects and mechanisms of berberine(BBR)on oxidized low-density lipoprotein(ox-LDL)-induced macrophage efferocytosis dysfunction and inflammatory response.Methods Using an ox-LDL-induced efferocytosis dysfunction model in human THP-1-derived macrophages,the cells were divided into the following groups:control,ox-LDL,ox-LDL+BBR(5,10,20 μmol/L),ox-LDL+BBR+ABC294640,ox-LDL+BBR+ABC294640+S1P,and ox-LDL+BBR+BIX02189 groups.The ox-LDL group was treated with 80 μmol/L ox-LDL for 24 h.In other groups,cells were pretreated with 80 μmol/L ox-LDL for 2 h,followed by co-incubation for 24 h with BBR,the SPHK2 inhibitor ABC294640(25 μmol/L),exogenous S1P(80 nmol/L),or the MEK5 inhibitor BIX02189(100 nmol/L),as required.Macrophage efferocytosis efficiency was assessed using fluorescence microscopy and flow cytometry.S1P levels were measured by ELISA.Protein expression levels of MerTK,AXL,TYRO3,SPHK1/2,MEK5,ERK5,and p-ERK5 were determined by Western blot.Results Compared with the control group,the ox-LDL group exhibited decreased efferocytosis efficiency(P<0.001,P<0.01),reduced protein expression levels of MerTK,AXL,TYRO3,MEK5,p-ERK5/ERK5,and SPHK2(P<0.01,P<0.001),and decreased S1P levels(P<0.01).Compared with the ox-LDL group,treatment with 20 μmol/L BBR significantly increased efferocytosis efficiency(P<0.01)and elevated protein expression levels of MerTK,AXL,TYRO3,MEK5,p-ERK5/ERK5,and SPHK2(P<0.05,P<0.01).Compared with the ox-LDL+20 μmol/L BBR group,the addition of ABC294640 decreased efferocytosis efficiency(P<0.01)and reduced protein expression levels of MerTK,AXL,TYRO3,MEK5,p-ERK5/ERK5,and SPHK2(P<0.05,P<0.01).Compared with the ox-LDL+20 μmol/L BBR+ABC294640 group,the addition of S1P increased efferocytosis efficiency(P<0.01,P<0.05)and elevated protein expression levels of MerTK,AXL,TYRO3,MEK5,p-ERK5/ERK5,and SPHK2(P<0.05,P<0.01).Compared with the ox-LDL+20 μmol/L BBR group,the addition of BIX02189 decreased efferocytosis efficiency(P<0.01)and reduced protein expression levels of MerTK,AXL,TYRO3,MEK5,and p-ERK5/ERK5(P<0.05,P<0.01).Conclusion BBR may exert its effects through the SPHK2/S1P/ERK5 pathway to alleviate ox-LDL-induced macrophage efferocytosis dysfunction.关键词
小檗碱/胞葬作用/巨噬细胞/鞘氨醇激酶 2/细胞外信号调节激酶 5/1-磷酸鞘氨醇Key words
berberine/efferocytosis/macrophage/sphingosine kinase 2/extracellular signal-regulated kinase 5/sphingosine-1-phosphate分类
医药卫生引用本文复制引用
付傲妮,刘婉婷,李婧,杨皓天,李朝荃,谢玉鑫,雷偲,易光辉..小檗碱通过SPHK2/S1P/ERK5通路对ox-LDL诱导的巨噬细胞胞葬功能障碍的影响[J].湖南中医药大学学报,2026,46(5):889-897,9.基金项目
国家自然科学基金项目(81770490) （81770490）
湖南省科技计划项目(2020JJ4535). （2020JJ4535）
