AcSDKP对大鼠矽肺纤维化转化生长因子-β1和结缔组织生长因子表达的抑制  

Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by regulation of transforming growth factor beta and connective tissue growth factor expression on rats with silicosis

作　　者：李倩[1] 杨方[1] 张丽娟[1] 闫静波[2] 陈萍[3] 李丹丹[1] 武鹍飞[1] 

机构地区：[1]华北煤炭医学院实验中心,唐山063000 [2]邢台市人民医院病理科 [3]天津泰达心血管病医院超声科

出　　处：《中华劳动卫生职业病杂志》2009年第7期390-394,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：人事部留学人员科技活动资助项目（国人厅发[2006]164号）;河北省自然科学基金资助项目（C2005000807）;唐山市新药基础研究重点实验室资助项目（04362001B-9）

摘　　要：目的探讨N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸（AcSDKP）对大鼠肺内转化生长因子（TGF）-β1、结缔组织生长因子（CTGF）表达的影响。方法将大鼠随机分为6组，每组10只。对照组大鼠支气管内灌注1．0ml生理盐水，矽肺模型对照1组4周后处死，矽肺模型对照2组8周后处死；矽肺模型组大鼠予SiO：混悬液50mg／ml，矽肺模型1组4周后处死，矽肺模型2组8周后处死；抗纤维化治疗组（治疗组）：支气管内灌注SiO：混悬液50mg／ml，4周后给予AcSDKP800μg／（kg·d），至第8周处死；预防治疗组给予AcSDKP800μg／（kg·d）48h后，支气管内灌注SiO：混悬液50mg／ml，8周后处死。HE染色进行形态学观察；采用免疫组织化学法检测TGF—β1与CTGF的蛋白表达；采用实时荧光定量聚合酶链反应（PCR）及反转录-聚合酶链反应（RT—PCR）法检测TGF-β1，与CTGF的mRNA表达。结果治疗组TGF-β1及CTGF蛋白表达分别为0．244±0．016、0．241±0．017，明显低于矽肺模型1组和矽肺模型2组；治疗组TGF-β1mRNA及CTGFmRNA表达水平明显低于矽肺模型1组和矽肺模型2组，差异均有统计学意义（P〈0．05）；预防治疗组TGF—β1和CTGF蛋白表达和mRNA表达水平明显低于矽肺模型2组，差异均有统计学意义（P〈0．05）。结论AcSDKP能减轻实验性矽肺纤维化大鼠肺组织中的TGF-β1与CTGF表达水平。Objective To investigate whether the effect of N-acetyl-seryl-aspartyl-lysyl-proline （AcSDKP） on transforrming growth factor beta （TGF-β1） and connective tissus growth factor （CTGF） was involved in AcSDKP＇s antifibrotic effect on the rats with silicosis. Methods Rats were divided into 6 groups randomly, 10 rats in each group： Control of silicotic model： 1.0 ml normal sodium and was killed after 4 or 8weeks; Silicotic model 1：50 mg/ml silica suspension and was killed after 4 weeks; Silicotic model 2：50 mg/ml silica suspension and was killed after 8 weeks; Anti-fibrosis treatment of AcSDKP： after each rat was intratracheally instilled with 50 mg/ml silica suspension for 4 weeks, AcSDKP 800 μg/（kg·d） was administered into every rat and rats were killed at the 8 weeks; Preventing fibrosis treatment of AcSDKP： after AcSDKP [800 μg/（kg·d） ] was administered into every rat for 48 hours, each rat was intratracheally instilled with 50 mg/ml silica suspension and rats were killed at the 8 weeks. Lung fibrosis in morphology was observed by HE staining. The expressions of TGF-β1 and CTGF in lung were observed by immunohistochemistry. The mRNA expressions of TGF-β1 and CTGF in lung were observed by real-time PCR. Results In anti-fibrosis treatment of AcSDKP group, protein expression of TGF-β1 and CTGF were （0.244±0.016） and （0.241±0.017）respectively, and significantly lower that those in the silicotic model 1 and 2 groups; mRNA expressions of TGF-β1 and CTGF decreased, mRNA expressions of CTGF were significantly lower that those in the silicotic model 1 and 2 groups（P〈0.05 ） ; In preventing fibrosis treatment of AcSDKP group, protein expression and mRNA expression of TGF-β1 were significantly lower that those in the silicotic model 2 group （P〈0.05）. Conclusion AcSDKP can decrease the expressions of TGF-β1 and CTGF in lung tissues of the rats with experimentally induced pulmonary fibrosis.

关 键 词：矽肺 肺纤维化 转化生长因子β 结缔组织生长因子 

分 类 号：R686[医药卫生—骨科学]