Ac⁃SDKP抑制SPP1/TGF⁃β1信号拮抗实验性矽肺的机制  

Ac⁃SDKP attenuates silicosis by inhibiting SPP1/TGF⁃β1 signaling

作　　者：蔡文臣 张诗汇 魏中秋 靳馥宇 李雅倩 李田 徐洪 杨方 CAI Wenchen;ZHANG Shihui;WEI Zhongqiu;JIN Fuyu;LI Yaqian;LI Tian;XU Hong;YANG Fang(School of Public Health,North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学临床医学院,河北唐山063210 [3]华北理工大学基础医学院,河北唐山063210

出　　处：《实用医学杂志》2021年第2期159-163,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:81972988);河北省自然科学基金资助项目(编号:H2020209052);河北省高等学校科学技术研究项目(编号:ZD2019077)。

摘　　要：目的探讨N⁃乙酰基⁃丝氨酰⁃天门冬酰⁃赖氨酰⁃脯氨酰(Ac⁃SDKP)通过调节分泌性磷蛋白1(SPP1)/转化生长因子1(TGF⁃β1)信号,从而抑制实验性矽肺的作用及其机制。方法Wistar大鼠分为对照24周组、矽肺24周组和Ac⁃SDKP治疗组。RWA264.7细胞分为对照组、SiO_(2)诱导组和SiO2+Ac⁃SDKP组;以及对照组、重组SPP1诱导组、SPP1+Ac⁃SDKP组和SPP1+LY364947组。免疫组织化学染色(IHC)检测SPP1的表达以及定位;免疫印迹法检测I型胶原(COL I)、巨噬细胞趋化蛋白⁃1(MCP⁃1)、TGF⁃β1、转化生长因子I型受体(TGFβRI)、TGFβRII、p⁃Smad2/3、Smad2/3和SPP1的表达。结果IHC及免疫印迹结果显示,与对照组比较,矽肺模型组COL I、MCP⁃1、TGF⁃β1和SPP1表达上调,与矽肺模型组比较,Ac⁃SDKP治疗组COL I、MCP⁃1、TGF⁃β1和SPP1的表达降低(P<0.05)。与对照组比较,SiO2诱导组COL I、MCP⁃1、TGF⁃β1和SPP1蛋白表达水平上调;与SiO2诱导组比较,Ac⁃SDKP组COL I、MCP⁃1、TGF⁃β1和SPP1蛋白表达水平下调(P<0.05)。与对照组比较,SPP1诱导组TGFβRI、TGFβRII和p⁃Smad2/3表达上调;与SPP1诱导组比较,Ac⁃SDKP组和LY364947组TGFβRI、TGFβRII和p⁃Smad2/3表达下调(P<0.05)。结论Ac⁃SDKP可以通过抑制SPP1/TGF⁃β1信号通路发挥抗矽肺纤维化的作用。Objective To investigate the effect and mechanism of N-acetyl-seranyl-aspartate-lysyl-proline(Ac-SDKP) in inhibiting experimental silicosis by regulating secreted phosphoprotein 1(SPP1)/transforming growth factor-β1(TGF-β1) signaling.Methods Wistar rats were randomly divided into control 24 week group,silicosis 24 week group and Ac-SDKP treatment group.RAW264.7 cells were divided into control group,SiO_(2) induced group and SiO2+Ac-SDKPtreated group.As well as control group,recombinant SPP1 induced group,SPP1+Ac-SDKP group and SPP1+LY364947 group.Immunohistochemical staining(IHC) was used to detect SPP1 expression and localization.The expression of COL I,monocyte chemoattractant protein-1(MCP-1),TGF-β1,TGF-β receptor type Ⅰ(TGFβ RⅠ),TGFβRⅡ,p-Smad2/3,Smad2/3 and SPP1 in lung tissue and RAW264.7 cells were measured by western blot.Results IHC and western blot results showed that compared with the control group,the expressions of COL I,MCP-1,TGF-β1 and SPP1 in the silicosis group were up-regulated,and the expressions of COL I,MCP-1,TGF-β1 and SPP1 in the Ac-SDKP group were decreased compared with the silicosis group(P <0.05).Compared with the control group,the protein expression levels of COL I,MCP-1,TGF-β1 and SPP1 were up-regulated in the SiO2-induced group.In addition,the expression levels of COL I,MCP-1,TGF-β1 and SPP1 in the Ac-SDKP treated group were down-regulated compared with SiO2-induced group(P <0.05).Compared with the control group,TGFβRⅠ,TGFβRⅡ andp-Smad2/3 were up-regulated in the SPP1 induced group.Compared with the SPP1 induced group,the expression of TGFβ RⅠ,TGFβ RⅡ andp-Smad2/3 were down-regulated in the Ac-SDKP group and LY364947 group(P <0.05).Conclusion Ac-SDKP can play a suppressing silicosis role by inhibiting the SPP1/TGF-1 signaling pathway.

关 键 词：矽肺纤维化 分泌性磷蛋白1 N⁃乙酰基⁃丝氨酰⁃天门冬酰⁃赖氨酰⁃脯氨酰 RAW264.7细胞 转化生长因子1 

分 类 号：R135.2[医药卫生—劳动卫生]