Smad3、Smad7在百草枯中毒大鼠肺成纤维细胞中的表达及红霉素对其影响  

Effects of erythromycin on expression of Smad3、Smad7 in lung fibroblasts from rats treated with paraquat

作　　者：李孝全[1] 何庆[2] 

机构地区：[1]湖北十堰市人民医院急诊科 [2]四川大学华西医院急诊医学科教授

出　　处：《世界急危重病医学杂志》2007年第5期2033-2034,共2页internationl journal of emergency and critical care medicine

摘　　要：[论文特点介绍]以红霉素为代表的大环内酯类抗生素中部分抗生素除了具有抗菌活性外，还具有非抗菌活性。本研究探讨红霉素除了通过调节炎症反应对百草枯中毒所致肺纤维化具有干预作用外，是否具有直接抗纤维化作用，是否对肺成纤维细胞的增殖和胶原的产生有直接的作用及其可能的机制。结果显示，推测红霉素对百草枯中毒导致的肺纤维化有干预作用，Backgroud and objective Paraquat intoxication is a common cause of death among toxicosis patients. Due to the lack of an antidote or effective treatment, there is a high mortality of the paraquat-intoxicated patients. Severe paraquat intoxication is characterized by multiple organ failure, and the lungs are the most important target organs. The lungs present with early persistent alveolitis followed by later progressively pulmonary fibrosis. TGF-β/Smad signaling plays an important role in the process of pulmonary fibrosis. It has been indicated that some of macrolides including erythro- mycin have the property of anti-inflammatory independent of anti-microbial activity. The present study was undertaken to investigate the anti-fibrosis effects of erythromycin on an experimental model of paraquat-induced lung fibrosis in rats. Methods Thirty SD rats were randomized to six groups： control group, paraquat group, erythromycin group, PQ＋EM pre-treatment group, PQ＋EM syn-treatment group and PQ＋EM post-treatment group. PQ was intra- gastrically administrated at a dose of 80 mg/kg for once to the rats in all groups except for the NS and EM groups on day 0. EM was intragastrically administrated at a dose of 50 mg/kg once a day to the rats in EM group, PQ＋EM pre-treatment group, PQ＋EM syn-treatment group and PQ＋EM post-treatment group from day 0, -3, 0, 7 to day 21 respectively. The rats in the NS group were intragastrically administrated equivalent volume of normal saline once a day. All the animals were sacrificed on day 21, and the lung specimens were obtained. The right upper lung was resected for measurement of collagen, the right lower lung was assessed histological. The left lung was obtained to establish primary lung fibroblasts culture. MTT method and hydroxyproline alkaline hydrolysis were applied to evaluate the fibroblasts proliferation and collagen production respectively. Immunohistochemistry was applied to detect Smad3, Smad7. In situ hybridization was applied to detect Smad3 mRNA, Smad7 mRNA.

关 键 词：肺成纤维细胞 百草枯中毒 红霉素 SMAD3 SMAD7 大环内酯类抗生素 大鼠 抗纤维化作用 

分 类 号：R135.2[医药卫生—劳动卫生] R595.4[医药卫生—公共卫生与预防医学]