N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对TGF-β1介导Smad通路调节在大鼠矽肺纤维化形成中的作用  

EFFECT OF N-ACETYL-SERYL-ASPARTYL-LYSYL-PROLINE ON PULMONARY FIBROSIS VIA INHIBITION OF TGF-β1-MEDIATED SMAD PATHWAY IN RATS WITH SILICOSIS

作　　者：杨方[1] 吉子言[1] 李丹丹[2] 李倩[1] 田景瑞[3] 魏中秋[1] 张丽娟[1] 王瑞敏[1] 

机构地区：[1]河北联合大学医学实验研究中心,唐山063000 [2]唐山市协和医院病理科 [3]河北理工大学

出　　处：《现代预防医学》2011年第23期4930-4932,4936,共4页Modern Preventive Medicine

基　　金：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);河北省科技支撑计划项目(09276198D);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)对大鼠矽肺纤维化肺组织中胶原含量、转化生长因子-β1(TGF-β1)、Smad2/3和Smad 7表达的调节,探讨AcSDKP拮抗矽肺纤维化的作用机制。[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,采用羟脯氨酸测量法和Western-blot法定量分析肺组织中胶原蛋白的含量。Western-blot法检测肺组织内TGF-β1、phospho-Smad2/3及Smad7蛋白的表达。[结果]AcSDKP治疗组胶原含量和I型、III型胶原的表达低于相对应的矽肺模型组。与相应的对照组相比,矽肺模型组大鼠肺组织内TGF-β1、phospho-Smad2/3蛋白表达均增加,而Smad7蛋白表达减弱。与相应矽肺模型组相比,给予AcSDKP后,大鼠肺组织内TGF-β1、phospho-Smad2/3蛋白表达表达均明显降低。而Smad7蛋白表达增强。[结论]AcSDKP可能是通过对TGF-β1介导Smad通路调节而发挥抗矽肺纤维化的作用。[Objective]We investigated that the effect of AcSDKP on the regulating expression of TGF-β1 and Smad2/3 and Smad 7 and content of collagen,to explore its mechanism on inhibition of pulmonary fibrosis in silicosis rats.[Methods]Rats were intratracheally instilled with silica as silicotic models,and administrated AcSDKP in these silicotic rats.The content of total collagen was detected by hydroxyproline assay.The expressions of type I and type III collagen,TGF-β1 and phospho-Smad2/3 and Smad7 were measured by Western blot.[Results]Compared with in silicotic model groups,the content of total collagen and expression of type I and type III collagen were decreased in AcSDKP treatment groups.Compared with the corresponding control groups,the expression of TGF-β1 and phospho-Smad2/3 increased and Smad 7 decreased in silicotic model groups.Compared with corresponding silicotic model groups,the expressions of TGF-β1 and phospho-Smad2/3 were decreased and Smad 7 increased obviously after administration of AcSDKP.[Conclusion]AcSDKP could inhibit TGF-β1-mediated Smad pathway,which is related with AcSDKP anti-silicosis role possibly.

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 SMAD2/3 SMAD7 矽肺 

分 类 号：R135.2[医药卫生—劳动卫生]