雷帕霉素对染尘大鼠肺组织胶原蛋白表达的影响  

Effects of rapamycin on collagen expression in lung tissue of silicosis model of rats

作　　者：张晓雪 王路遥 李宁 宋瑞瑞 时亚欣 李清钊 沈福海 蒋守芳 金玉兰 ZHANG Xiao-xue;WANG Lu-yao;LI Ning;SONG Rui-rui;SHI Ya-xin;LI Qing-zhao;SHEN Fu-hai;JIANG Shou-fang;JIN Yu-lan(School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000,Chin)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063000

出　　处：《环境与健康杂志》2017年第12期1071-1074,F0003,共5页Journal of Environment and Health

基　　金：国家自然科学基金(81202161);教育部重点项目(212013)

摘　　要：目的探讨雷帕霉素对染矽尘大鼠肺组织胶原蛋白表达的影响。方法对50只SPF级健康雄性大鼠建立肺纤维化模型,随机分为模型组和雷帕霉素组,两组均一次性气管灌注二氧化硅(250 mg/kg);同时,分别腹腔注射生理盐水和雷帕霉毒[2μg/(kg·d)],均隔天给药,持续28 d,分别于第7、14、28、60、90天,用酶联免疫法测定血清中肿瘤坏死因子α(TNF-α)、转化生长因子β(TGF-β)含量,用Massson染色观察大鼠肺组织病理组织学变化,用q RT-PCR法测定肺组织中Ⅰ型和Ⅲ型胶原m RNA含量。结果大鼠肺组织Massson染色结果显示,雷帕霉素组大鼠肺纤维化较模型组严重。随着时间的延长,模型组大鼠血清中TNF-α和TGF-β逐渐升高,差异有统计学意义(P<0.05)。雷帕霉素组大鼠血清中TNF-α和TGF-β随着时间的延长而升高,在60 d时降低,90 d时再次升高;除60 d外,其他时间均高于模型组(P<0.05)。随着时间的延长,模型组大鼠肺组织Ⅰ、Ⅲ型胶原m RNA逐渐升高,且差异有统计学意义(P<0.05)。雷帕霉素组大鼠肺组织Ⅰ、Ⅲ型胶原m RNA表达随各时间点呈降低-升高波动趋势,其中Ⅰ型胶原m RNA表达在除60 d外的各时间点均高于模型组,Ⅲ型胶原m RNA表达在7、28、90 d高于模型组,差异有统计学意义(P<0.05)。结论雷帕霉素后期给药可能通过抑制m TOR信号通路而加重染尘大鼠的肺组织纤维化程度。Objective To observethe effects of rapamycin on collagen expression in lung tissue of silicosis model of rats.Methods A total of 50 male Wistar rats were randomly divided into two groups： silicosis model group and rapamycin group,the two groups were all treated with intratracheal instillation of silicon dioxide at first,then were treated with intraperitoneal injection of normal saline and rapamycin [2 μg/（kg·d）] respectively, twice a day for 28 days.The levels of TNF-ɑ, TGF-β in serum were determined by ELISA,the m RNA levels of collagen Ⅰ and collagen Ⅲ were measured by q RT-PCR,the pathological changes in lung tissue of rats were observed by Masson staining, atthe 7th, 14th, 28th, 60th and 90th day ofthe experiment. Results The pulmonary fibrosis,observed by Massson staining, in lung tissue of rats in rapamycin group rats was more serious compared withthe silicosis model group.In silicosis model group,the contents of TNF-ɑ and TGF-β in serum increased with exposure time,and showed significant differences during observation period（P 〈0.05）. In rapamycin group,the levels of TNF-ɑ and TGF-βin serum increased with exposure time（7-28 d）, decreased atthe 60th day, andthen increased atthe 90th day;Compared withthe silicosis model group,the levels of TNF-ɑ and TGF-βin serum increased at each observation day exceptthe 60th day,and revealed significanly difference atthe 14th, 28th and 90th day ofthe experiment（P〈0.05）. The m RNA levels of collagend Ⅰ and Ⅲ in silicosis model group showed a time-dependent manner,increased with exposure time,and showed significant differences during observation period（P〈0.05）; In rapamycin group,they revealed a trend of fluctuations,decraesed first andthen increased. In rapamycin group,the m RNA levels were significantly higher at each observation day exceptthe 60th day ofthe experiment for collagendⅠ, and atthe 7th、28th、90th day for collagend Ⅲ, compared withthose in silicosis model group（P 〈0.05）. Conclusion Delayed treatment by

关 键 词：肺纤维化 雷帕霉素 胶原纤维 

分 类 号：R994.6[医药卫生—毒理学]