PM_(2.5)通过氧化应激对人支气管上皮细胞JAK/STAT信号通路的影响  

Effect of PM_(2. 5) on oxidative stress-JAK/STAT signaling pathway of human bronchial epithelial cells

作　　者：徐贞贞[1] 张志红[1] 马晓燕[1] 平飞飞 郑鑫[1] 

机构地区：[1]山西医科大学公共卫生学院环境卫生学教研室,太原030001

出　　处：《卫生研究》2015年第3期451-455,共5页Journal of Hygiene Research

基　　金：山西省回国留学人员科研资助项目(No.2013-057);教育部留学回国人员科研启动基金(No.教外司留(2013)1792号)

摘　　要：目的探讨PM2.5通过氧化应激对人支气管上皮细胞JAK/STAT信号通路和细胞因子的影响。方法利用传统侵入式方法培养支气管上皮细胞16HBE,本次研究共从两方面来进行探讨:(1)探讨PM2.5、氧化应激与JAK/STAT信号通路的关系,设立生理盐水对照组、N-乙酰-L-半胱氨酸(NAC,5 mmol/L)组、50μg/ml PM2.5组、100μg/ml PM2.5组、50μg/ml PM2.5+5 mmol/L NAC组和100μg/ml PM2.5+5mmol/L NAC组,培养24 h后测定细胞内ROS水平和JAK2、STAT3的基因表达。(2)探讨PM2.5、JAK/STAT信号通路和细胞因子的关系,设立生理盐水对照组、6μmol/L AG490组、100μg/ml PM2.5组、6μmol/L AG490+100μg/ml PM2.5组,培养24 h后检测细胞上清液中白介素-6(IL-6)含量。结果染毒24 h后,50μg/ml PM2.5组和100μg/ml PM2.5组16HBE细胞内ROS水平和JAK2、STAT3基因表达均高于生理盐水对照组,PM2.5暴露+NAC保护组ROS水平和JAK2、STAT3的基因表达均低于各自PM2.5暴露组,差异均有统计学意义(P<0.05)。100μg/ml PM2.5组上清液中IL-6含量高于生理盐水对照组,6μmol/L AG490+100μg/ml PM2.5组细胞上清液中IL-6含量低于100μg/ml PM2.5暴露组,差异均有统计学意义(P<0.05)。结论 PM2.5能对支气管上皮细胞造成氧化损伤,并可能通过氧化应激调节上皮细胞JAK/STAT信号通路和相关细胞因子的产生。Objective To investigate the regulation of oxidative stress-JAK/STAT signaling pathway on cytokines in human bronchial epithelial cells induced by PM2.5. Methods Bronchial epithelial cells 16HBE were cultured using traditional invasive methods. Two aspects were explored , one is the relationship among PM2.5, oxidative stress, JAK/STAT signaling pathway. There were the following groups,control group, N- acetyl-L-cysteine （ NAC,5 mmol/L） group, 50 μg/ml PM2.5 group, 100 μg/ml PM2.5 group,50μg/ml PM2.5 ＋ 5 mmol/L NAC group, 100 μg/ml PM2.5 ＋ 5 mmol/L NAC group. Intracellular ROS levels and the gene expression of JAK2 and STAT3 were detected after all groups were exposed for 24 h. The other one is to explore the relationship among PM2.5, JAK/STAT signaling pathway and cytokine. The groups were arranged the following, control group,6 μmol/L AG490 group, 100 μg/ml PM2.5 group, 6 μmol/L AG490 ＋ 100 μg/ml PM2.5 group. The level of IL-6 was determined after all groups were exposed for 24h. Results After 24 h exposure, intracellular ROS levels and the gene expression of JAK2 and STAT3 in 50 μg/ml PM2.5, 100 μg/ml PM2.5 exposure group were higher than the control group. Intracellular ROS levels and the gene expression of JAK2 and STAT3 in PM2.5 ＋ NAC protection group were lower than the respective PM2.5 exposure group, the differences were statistically significant （P 〈 0. 05 ）. IL-6 levels of cellular supernatant in 6 μmol/L AG490 ＋ 100 μg/ml PM2.5 group were lower than 100μg/ml PM2.5 group, the differences were statistically significant （ P 〈 0.05 ）. Conclusion PM2.5 could cause oxidative damage on bronchial epithelial cells, and then regulate JAK/STAT signaling pathway and relative cytokines of epithelial cells through oxidative stress.

关 键 词：PM2.5 氧化应激 JAK/STAT 白介素-6 

分 类 号：R994.6[医药卫生—毒理学] Q593[医药卫生—药学]