p38 MAPK在喹乙醇诱导HepG2细胞凋亡中的作用  

Effects of p38 MAPK signaling pathway on apoptosis stimulated by olaquindox in human hepatoma G2 cells

作　　者：赵文霞[1] 张朝明[1] 汤树生[1] 张婷[1] 孙雨[1] 靳溪[1] 肖希龙[1] 

机构地区：[1]中国农业大学动物医学院药理和毒理教研室,北京100193

出　　处：《癌变．畸变．突变》2012年第1期10-13,19,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：中央高校基本科研业务费专项资金(2011JS009)

摘　　要：目的:研究p38 MAPK信号通路在喹乙醇诱导的HepG2细胞凋亡中的作用。方法:分别用不同浓度(0、200、400、800μg/ml)的喹乙醇染毒HepG2细胞24 h和800μg/ml喹乙醇染毒HepG2细胞不同时间(0、0.5、1、2、4、6、12、24 h)后,采用Westernblot法检测细胞内磷酸化p38蛋白和p38总蛋白的表达情况,以p38 MAPK磷酸化水平反映p38 MAPK信号通路的活性。分别采用0、10、20μmol/L的p38 MAPK特异性抑制剂SB203580预处理HepG2细胞1 h后,再用800μg/ml喹乙醇染毒24 h,采用Annexin VFITC/PI法检测细胞凋亡。结果:随着喹乙醇染毒浓度和时间的增加,HepG2细胞的p38磷酸化蛋白表达量逐步增加,其中800μg/ml喹乙醇染毒细胞24 h的实验组与对照组相比,p38磷酸化蛋白的表达量明显上调(P<0.01)。10、20μmol/L的SB203580对喹乙醇诱导细胞凋亡有促进作用,细胞的凋亡率分别为35.4%±2.83%、40.2%±3.98%,较喹乙醇对照组(23.1%±3.59%)明显升高(P<0.05)。结论:喹乙醇能激活p38 MAPK信号通路,且p38 MAPK信号通路的激活参与抑制喹乙醇介导的HepG2细胞凋亡的过程。OBJECTIVE：To investigate the effect of p38 MAPK signaling pathway on the apoptosis induced by olaquindox in human hepatoma G2（HepG2） cells.METHODS：The HepG2 cells were treated with different concentrations（0,200,400,800μg/ml） of olaquindox for 24 h or with 800 p,g/ml olaquindox for different time points （0,0.5,1,2,4,6,12,24 h）.Then the expression of p38 and phosphorylation of p38（p-p38） were determined by Western blot.The HepG2 cells which were pretreated with different concentrations（0,10,20μmol/L） of SB203580 for 1 h were subsequently treated with 800μg/ml olaquindox for 24 h.The changes of apoptosis were analyzed by Annexin VFITC and propidium iodide（PI） staining.RESULTS：The expression of p-p38 increased gradually with the dose and time of olaquindox treatment.Moreover,compared with control group,the expression of p-p38 was observably apparent with the treatment of 800μg/ml olaquindox for 24 h（P0.01）.Compared with olaquindox control group （23.1%±3.59%）,the apoptosis of olaquindox-treated HepG2 cells was enhanced by different concentrations（10,20μmol/L） of SB203580 with the apoptotic rate of 35.4%±2.83%and 40.2%±3.98%respectively（P0.05）. CONCLUSION：p38 MAPK signaling pathway was activated by olaquindox,which played a role in inhibiting apoptosis induced by olaquindox-treated HepG2 cells.

关 键 词：喹乙醇 P38 MAPK 细胞凋亡 HEPG2细胞 

分 类 号：R991[医药卫生—毒理学]