N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对矽肺大鼠肺内P38信号转导通路蛋白表达的调节  

Effect of AcSDKP on the expression of TGF-β1 and P38 MAPK in the lung of rats with silicosis

作　　者：魏中秋[1] 杨方[1] 田景瑞[1,2] 冯海利[1] 李治国[1] 王瑞敏[1] 

机构地区：[1]华北煤炭医学院实验中心,河北唐山063000 [2]河北理工大学图书馆,唐山063000

出　　处：《中国职业医学》2010年第1期8-12,共5页China Occupational Medicine

基　　金：河北省科技支撑计划项目(40224954-6);中华人民共和国人事部留学人员科技活动基金(国人厅发[2006]164号);河北省自然科学基金(C2005000807);唐山市新药基础研究重点实验室项目(04362001B-9)

摘　　要：目的观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对大鼠矽肺纤维化模型Ⅰ型胶原、Ⅲ型胶原、转化生长因子-β1(TGF-β1)与P38分裂原活化蛋白酶(MAPK)蛋白表达的影响,探讨AcSDKP拮抗矽肺纤维化可能的作用机制。方法选用非暴露式气管灌注法制作大鼠矽肺模型,并给予AcSDKP。免疫组化法、Western-blot法检测肺组织内Ⅰ型胶原、Ⅲ型胶原、TGF-β1、磷酸化P38 MAPK(phospho-P38 MAPK)、P38 MAPK蛋白的表达。结果与对照组相比,矽肺模型组大鼠肺组织内Ⅰ型胶原、Ⅲ型胶原、TGF-β1、phospho-P38 MAPK蛋白表达均增加;与矽肺模型组相比,AcSDKP治疗后,大鼠肺组织内Ⅰ型胶原、Ⅲ型胶原、TGF-β1、phospho-P38 MAPK蛋白表达均明显降低。而各组间比较,P38 MAPK蛋白表达无明显改变。结论AcSDKP可能通过抑制TGF-β1介导的P38 MAPK信号转导途径,从而发挥抗矽肺纤维化的作用。Objective To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline（AcSDKP） on the expressions of collagen typeⅠand type Ⅲ,TGF-β1 and P38 mitogen-activated protein kinase（MAPK） in the lung of rats with silicosis.Methods As the silicotic models,rats were instilled with silica through trachea and then administrated with AcSDKP.The expressions of collagen type Ⅰ and type Ⅲ,TGF-β1,phospho-P38 MAPK and P38 MAPK were detected by immunohistochemistry and western blot assay.Results In comparison with the corresponding control groups,the expressions of collagen type Ⅰand type Ⅲ,TGF-β1 and phospho-P38 MAPK increased in the lung tissue of the silicotic models.Compared with the corresponding model groups,the expressions of collagen type Ⅰand type Ⅲ,TGF-β1 and phospho-P38 MAPK in the lung tissue obviously reduced after administration AcSDKP.The expression of P38 MAPK was not significantly changed among all groups.Conclusion AcSDKP could play an important role in anti-silicotic fibrosis by inhibiting TGF-β1 mediated P38 MAPK signal transduction pathway.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 转化生长因子-Β1 矽肺 P38分裂原活化蛋白酶 大鼠 纤维化 

分 类 号：R135.2[医药卫生—劳动卫生]