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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(250mg/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qRT-PCR法测定肺组织中Ⅰ型和Ⅲ型胶原mRNA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-d和TGF-β随着时间的延长而升高,在60d时降低,90 d时再次升高;除60d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mRNA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mRNA表达随各时间点呈降低-升高波动趋势,其中Ⅰ型胶原mRNA表达在除60d外的各时间点均高于模型组,Ⅲ型胶原mRNA表达在7、28、90d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mTOR信号通路而加重染尘大鼠的肺组织纤维化程度.“,”Objective To observe the 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-α,TGF-β in serum were determined by ELISA,the mRNA levels of collagen Ⅰ and collagen Ⅲ were measured by qRT-PCR,the pathological changes in lung tissue of rats were observed by Masson staining,at the 7th,14th,28th,60th and 90th day of the experiment.Results The pulmonary fibrosis,observed by Massson staining,in lung tissue of rats in rapamycin group rats was more serious compared with the silicosis model group.In silicosis model group,the contents of TNF-a 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-α and TGF-βin serum increased with exposure time (7-28 d),decreased at the 60th day,and then increased at the 90th day;Compared with the silicosis model group,the levels of TNF-α and TGF-βin serum increased at each observation day except the 60th day,and revealed significanly difference at the 14th,28th and 90th day of the experiment (P＜0.05).The mRNA 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 and then increased.In rapamycin group,the mRNA levels were significantly higher at each observation day except the 60th day of the experiment for collagend Ⅰ,and at the 7th、28th、90th day for collagend Ⅲ,compared with those in silicosis model group (P＜0.05).Conclusion Delayed treatment by rapamycin,MTOR signaling pathway inhibitor,can significantly promote the development of silicosis fibrosis in rats.