摘要
目的探讨肝X受体(LXR)-三磷酸腺苷结合盒转运体A1(ABCA1)信号通路在游离二氧化硅(SiO2)诱导肺泡巨噬细胞泡沫化中的作用。方法采用豆蔻酸佛波醇乙酸酯将人淋巴组织瘤细胞株U937细胞诱导分化为巨噬细胞。将对数生长期巨噬细胞随机分为4组,对照组细胞不给予任何处理,SiO2刺激组细胞予剂量为50 mg/L的SiO2混悬液刺激,氧化低密度脂蛋白(ox-LDL)组细胞予剂量为50 mg/L的ox-LDL刺激,联合组细胞同时予剂量均为50 mg/L的SiO2混悬液和ox-LDL刺激。培养48 h后收集细胞,采用油红O染色法观察巨噬细胞泡沫化情况,采用酶标仪检测巨噬细胞中总胆固醇(TC)、游离胆固醇(FC)、胆固醇脂(CE)水平和CE比重,采用免疫印迹法检测细胞中LXR和ABCA1蛋白的表达。结果油红O染色结果显示,SiO2刺激组、ox-LDL组和联合组巨噬细胞均发生泡沫化改变,联合组巨噬细胞泡沫化程度高于其余2组。与对照组比较,SiO2刺激组、ox-LDL组、联合组巨噬细胞中TC、FC、CE水平和CE比重均升高(P<0.05),LXR和ABCA1蛋白相对表达水平均下降(P<0.05)。联合组巨噬细胞转化为泡沫细胞。与SiO2刺激组和ox-LDL组比较,联合组巨噬细胞中TC、FC、CE水平和CE比重均升高(P<0.05),LXR和ABCA1蛋白相对表达水平均下降(P<0.05)。结论游离SiO2可诱导巨噬细胞泡沫化,ox-LDL对此具有协同促进作用;该过程可能是通过抑制LXR-ABCA1信号通路实现。
Objective To investigate the effect of liver X receptor(LXR)-adenosine triphosphate-binding cassette transporter A1(ABCA1)signaling pathway on the free silica(SiO2)-induced foaming of macrophages.Methods Human histiocytic lymphoma U937 cells were induced to differentiate into macrophages by phorbol myristate acetate.The macrophages at logarithmic growth phase were randomly divided into 4 groups:the cells in the control group received no treatment,the cells in the SiO2 stimulation group were stimulated with SiO2 suspension at a dose of 50 mg/L,and the cells in the oxidized low-density lipoprotein(ox-LDL)group were treated with ox-LDL at the dosed 50 mg/L,the cells in the combination group were simultaneously stimulated with SiO2 suspension and ox-LDL at a dose of 50 mg/L.Cells were collected after 48 hours of culture.Macrophage foaming was observed by oil red O staining.The levels of total cholesterol(TC),free cholesterol(FC),cholesteryl ester(CE)and CE specific gravity(CE%)in macrophages were detected using a microplate reader.The expression of LXR and ABCA1 was detected using Western blotting.Results The results of the oil red O staining showed that all the macrophages in the SiO2 stimulation group,ox-LDL group and the combination group had foaming changes.The degree of foaming in the macrophages in the combination group was higher than that in the other two groups.The levels of TC,FC,CE and CE%in macrophages increased(P<0.05),and the protein relative expression of LXR and ABCA1 decreased(P<0.05),in SiO2 stimulation group,ox-LDL group and combination group compared with the control group.The macrophages in the combination group were transformed into foam cells.The levels of TC,FC,CE and CE%in macrophages of the combination group increased(P<0.05),and the protein relative expression of LXR and ABCA1 decreased(P<0.05),compared with the SiO2 stimulation group and the ox-LDL group.Conclusions Free SiO2 can induce foaming of macrophages,and ox-LDL in combination with SiO2 has a synergistic effect on the formation of foaming of macrophages.The process of macrophage foaming may be achieved by inhibiting the LXR-ABCA1 signaling pathway.
作者
徐秋敏
崔洁
王爽
李欣颖
张劲松
郭灵丽
郝小惠
王宏丽
刘和亮
XU Qiumin;CUI Jie;WANG Shuang;LI Xinying;ZHANG Jinsong;GUO Lingli;HAO Xiaohui;WANG Hongli;LIU Heliang(School of Public Health,North China University of Technology,Tangshan,Hebei 063210,China;不详)
出处
《中国职业医学》
CAS
北大核心
2020年第2期129-134,共6页
China Occupational Medicine
基金
国家自然科学基金资助项目(81673119)
河北省自然科学基金资助项目(H2018209337)
河北省卫计委医学科学研究重点课题计划(20160720)。
关键词
二氧化硅
巨噬细胞
泡沫细胞
胆固醇
胆固醇脂
肝X受体
三磷酸腺苷结合盒转运体A1
信号通路
Silica
Macrophages
Foam cell
Cholesterol
Cholesteryl ester
Liver X receptor
Adenosine triphosphate binding cassette transporter A1
Signaling pathway
