PM_(2.5)短期高浓度暴露及停止暴露对大鼠肺组织的影响  

Effects of short-term exposure and cessation of exposure to high concentration of PM_(2.5) on lung tissues in rats

作　　者：刘宇 胥嘉钰 张桥鉴 赵琳 刘芳盈[3] 邢燕[3] 阎腾龙 胡贵平 陈章健[1] 陈田 贾光[1] LIU Yu;XU Jia-yu;ZHANG Qiao-jian;ZHAO Lin;LIU Fang-ying;XING Yan;YAN Teng-long;HU Gui-ping;CHEN Zhang-jian;CHEN Tian;JIA Guang(Department of Occupational and Environmental Health Sciences,School of Public Health,Peking University 9 Beijing 100083,China;Department of Occupational and Environmental Health Sciences,School of Public Health,Shandong University,Jinan Shandong 250012,China;Center for Disease Control and Prevention,Zibo Shandong 255026,China;School of Medical Science and Engineeringy Beihang University,Beijing 100191,China;School of Public Health and Beijing Key Laboratory of Environmental Toxicology,Capital Medical University,Beijing 100069,China)

机构地区：[1]北京大学公共卫生学院劳动卫生与环境卫生学系,北京100083 [2]山东大学公共卫生学院职业与环境健康学系,山东济南250012 [3]淄博市疾病预防控制中心,山东淄博255026 [4]北京航空航天大学医学科学与工程学院,北京100191 [5]首都医科大学公共卫生学院首都医科大学环境毒理学北京市重点实验室,北京100069

出　　处：《毒理学杂志》2022年第2期113-118,共6页Journal of Toxicology

基　　金：国家自然科学基金(91743114)。

摘　　要：目的探讨PM_(2.5)短期高浓度暴露及停止暴露对大鼠肺组织炎症和纤维化相关标志物的影响。方法采集冬季北方某典型复合污染区PM_(2.5)并进行成分分析。32只SD雄性大鼠随机分为PM_(2.5)暴露组和空白滤膜对照组,每组16只。暴露组气管滴注超纯水洗脱的PM_(2.5),每次15 mg/kg·bw,每3 d暴露1次,持续30 d;对照组滴注等量超纯水洗脱的空白滤膜。末次染毒后每组随机处死一半大鼠,剩余大鼠停止暴露,恢复15 d后处死,取肺组织,分别进行病理和相关指标的检测。根据病理切片苏木素-伊红(HE)和Masson染色进行肺泡炎和纤维化评价;通过RT-qPCR检测肺组织炎性因子(IL-6、IL-1β、TNF-α和MCP-1)和纤维化指标(CollagenⅠ、TGF-β和PDGF)的转录水平。结果PM_(2.5)短期高浓度暴露后肺组织形态学显示肺泡炎程度加重,差异有统计学意义(P>0.05),炎性因子转录水平无明显改变(P>0.05);恢复15 d后,与同期对照组相比,暴露组肺泡炎分级差异无统计学意义(P>0.05),IL-6的mRNA表达量明显升高(P<0.05),其余炎性因子均呈现下降趋势,差异有统计学意义(P>0.05)。纤维化结果显示,PM_(2.5)暴露后肺组织胶原纤维含量明显增多(P<0.05),纤维化指标的mRNA水平均无明显改变(P>0.05);恢复15 d后,暴露组在组织层面恢复到对照组水平(P>0.05),CollagenⅠ转录水平比恢复前明显上升(P<0.05),TGF-β则明显下降(P<0.05);与同期对照组相比,暴露恢复组的CollagenⅠ和PDGF的mRNA水平均明显上升,差异有统计学意义(P<0.05)。结论PM_(2.5)短期高浓度暴露会引起大鼠肺部炎症和胶原纤维升高,停止暴露后,组织层面得到恢复,相关因子表达降低,但部分标志物的持续表达提示PM_(2.5)暴露存在后期效应。Objective To explore the effects of short-term exposure and cessation of exposure to high concentration of PM_(2.5)on markers related to inflammation and fibrosis in lung tissue of rats.Methods PM_(2.5)from a typical compound pollution area in North China in winter was collected and analyzed.Thirty-two SD male rats were randomly divided into PM_(2.5)exposure group and blank filter membrane control group,with 16 rats in each group.The exposed group was received intratracheal instillation of PM_(2.5)eluted by ultrapure water,15 mg/kg·bw each time,once every 3 days for 30 days.The control group was dripped with the same amount of blank filter membrane eluted with ultrapure water.After the last exposure,half of the rats in each group were randomly killed,the remaining rats stopped exposure,killed after 15 days of recovery.Lung tissues were taken for pathological and related indexes.Pulmonary alveolitis and fibrosis were evaluated by HE staining and Masson staining.The transcriptional levels of inflammatory factors(IL-6,IL-1β,TNF-αand MCP-1)and fibrosis markers(CollagenⅠ,TGF-βand PDGF)in lung tissue were measured by RT-qPCR.Results Pulmonary histomorphology showed that the grade of pulmonary alveolitis was aggravated after short-term exposure to high concentration of PM_(2.5)(P>0.05),and the transcriptional levels of inflammatory factors had no significant change(P>0.05).After 15 days of recovery,compared with the control group in the same period,there was no significant difference in the grade of pulmonary alveolitis in the exposure group(P>0.05),the mRNA expression of IL-6 increased significantly(P<0.05),and the other inflammatory factors showed a downward trend(P>0.05).The result of fibrosis showed that the content of collagen fibers in lung tissue increased significantly after PM_(2.5)exposure(P<0.05),and the mRNA levels of fibrosis markers did not change significantly(P>0.05).After 15 days of recovery,the exposure group recovered to the level of the control group at the tissue level(P>0.05),the transcriptio

关 键 词：PM_(2.5)大鼠 气管滴注 肺纤维化 肺泡炎 自我恢复 

分 类 号：R994.6[医药卫生—毒理学] R114[医药卫生—药学]