TGF-β_1/Smads信号通路对PM2.5致大鼠肺组织损伤的免疫调控作用  

Immunoregulation of TGF-β_1/Smads signal transduction pathway on rat lung impairment induced by PM2.5

作　　者：武洁[1,2] 杨晓君[3,4] 王晶[2] 刘晶[2] 卢军[2] 程路峰[1] 

机构地区：[1]新疆医科大学基础医学院药理学教研室,乌鲁木齐830011 [2]新疆医科大学附属中医医院,乌鲁木齐830006 [3]中国科学院新疆理化技术研究所,乌鲁木齐830011 [4]新疆农业大学食品科学与药学学院,乌鲁木齐830052

出　　处：《西北药学杂志》2017年第3期316-321,共6页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金地区科学基金项目(编号:81360491)

摘　　要：目的研究TGF-β_1/Smads信号通路在PM2.5细颗粒致大鼠肺组织损伤的免疫调控作用。方法将40只正常成年Wistar大鼠随机分为4组:空白对照组(Ctrl)、假手术组(Sham)、染毒组(PM2.5)及染毒+SB431542组(PMSB)。Sham组行假手术并给予生理盐水,PM2.5和PMSB组均给予PM2.5混悬液(15mg·kg^(-1))染毒,PMSB组于染毒前30min给予TGF-β_1阻断剂SB431542。12d后,收集左肺泡灌洗液及血清,分别检测肺泡灌洗液炎性细胞计数、血清IL-6、IL^(-1)7a和TGF-β_1,另取右肺组织测定Smad2、TGF-β_1、RORγt、FoxP3等基因的表达。结果 PM2.5组血清IL-6、IL^(-1)7a和TGF-β_1明显高于其余3组(P<0.05),但Ctrl、Sham和PMSB 3组间无明显差异(P>0.05)。在Smad2、TGF-β_1、RORγt和FoxP3基因表达方面,结果也与其一致。相关性分析:肺组织Smad2 mRNA含量与血清中IL-6、IL^(-1)7a和TGF-β_1呈正相关,RORγt mRNA水平与血清IL-6、IL^(-1)7a、TGF-β_1表达呈正相关,Foxp3mRNA水平与血清IL-6、IL^(-1)7a、TGF-β_1表达呈正相关。结论大气细颗粒物PM2.5能够引起大鼠肺组织损伤,其损伤程度随染毒剂量的增加而加重。其可能的主要机制是TGF-β_1表达增强,刺激肺部Smad2、RORγt和FoxP3表达,激发机体的免疫反应,使得血液中促炎性细胞因子IL-6、IL^(-1)7a、TGF-β_1增多,从而导致组织的免疫炎性损伤。Objective To explore the immunoregulation of TGF-β1/Smads signaling pathway on rat lung impairment induced by PM2.5.Methods 40 adult Wistar rats were randomly divided into 4groups：control group（Ctrl）,sham group（sham）,PM2.5group（PM2.5）,and PM2.5＋SB431542group（PMSB）.Sham group were treated with operation and saline,while both PM2.5and PMSB groups were exposed to PM2.5suspension（15mg·kg-1）,and PMSB group was injected SB431542 ip30 min before operation.After 12 days,aliveolar lavage saline was collected from left lung to measure IL-6,IL-17 aand TGF-β1levels;and the gene expressions of Smad2,TGF-β1,RORγt and FoxP3 were detected in right lung.Results IL-6,IL-17 aand TGF-β1in alveolar lavage fluid and serum of PM2.5group were significantly higher than the other 3groups（P〈0.05）,while there were no significant difference among Crtl,sham and PMSB groups（P〉0.05）.Gene expressions of Smad2,TGF-β1,RORγt and FoxP3 showed the similar results to the above.Correlation between the mRNA levels of Smad2,RORγt,Foxp3 and the contents of IL-6,IL-17 a and TGF-β1in serum was analyzed.The Smad2 mRNA was positively correlated with the expression level of IL-6,IL-17 aand TGF-β1in serum,The RORγt mRNA was positively correlated with the expression level of IL-6,IL-17 aand TGF-β1in serum.The Foxp3 mRNA was positively correlated with the expression level of IL-6,IL-17 aand TGF-β1in serum.Conclusion Lung injury in rats can be induced by atmospheric PM2.5in dose-dependent way.The underlying mechanism of lung injury induced by atmospheric PM2.5may be the accumulation of proinflammatory cytokines of IL-6,IL-17 aand TGF-β1,which were the consequence of activating expression of Smad2,RORγt and Foxp3 resulted from the increased expression of TGF-β1.

关 键 词：PM2.5细颗粒 肺损伤 IL-6 TGF-β1 SMAD2 

分 类 号：R965[医药卫生—药理学]