Ac-SDKP抑制YEATS4拮抗实验性矽肺的机制  

N-acetyl-seranyl-aspartate-lysyl-proline Attenuates Silicosis by Inhibiting YEATS4

作　　者：蔡文臣 张诗汇 高一冰 牛婉丽 徐洪 杨方 CAI Wenchen;ZHANG Shihui;GAO Yibing;NIU Wanli;XU Hong;YANG Fang(School of Public Health,North China University of Science and Technology,Tangshan 063210,China;School of Clinical Medicine,North China University of Science and Technology,Tangshan 063210;the Hebei Key Laboratory for Organ Fibrosis,Tangshan 063210)

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]河北省器官纤维化重点实验室,河北唐山063210

出　　处：《中国比较医学杂志》2021年第5期22-27,共6页Chinese Journal of Comparative Medicine

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

摘　　要：目的研究N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酰(N-acetyl-seranyl-aspartate-lysyl-proline,AcSDKP)通过调节含YEATS结构域蛋白4(YEATS domain containing protein 4,YEATS4)从而抑制矽肺纤维化的作用及其机制。方法 RAW264.7细胞分为si RNA阴性对照组(si RNA-Control,si C)、si RNA-YEATS4组(siY)、SiO_(2)+si RNA阴性对照组(S+si C)和SiO_(2)+si RNA-YEATS4组(S+siY);以及对照组(Control,C)、SiO_(2)诱导组(SiO_(2),S)、SiO_(2)+Ac-SDKP处理组(SiO_(2)+Ac-SDKP,S+Ac)和Ac-SDKP处理组(Ac)。Wistar大鼠分为对照24周组(Control 24week,C24)、矽肺24周组(Silicosis 24 week,S24)和Ac-SDKP治疗组(Ac-SDKP treatment 24 week,Ac24)。免疫印迹法(Western blot)检测I型胶原(Collagen type I,COL I)、巨噬细胞趋化蛋白-1(Monocyte chemoattractant protein-1,MCP-1)、精氨酸酶-1(Arginase-1)和YEATS4的表达。免疫组织化学染色法(Immunohistochemical staining,IHC)检测YEATS4在肺组织中的定位及表达。结果 Western blot结果显示,在RAW264.7细胞中,分别与si C、S+si C组比较,siY组、S+siY组COL I、MCP-1、Arginase-1表达均明显降低(P<0.05);与C组比较,S组COL I、MCP-1、Arginase-1和YEATS4高表达;与S组比较,S+Ac组中COL I、MCP-1、Arginase-1和YEATS4表达降低(P <0.05)。IHC及Western blot结果显示,与C24组大鼠比较,S24组中COL I、MCP-1、Arginase-1和YEATS4表达上调;与S24组比较,Ac24组中COL I、MCP-1、Arginase-1和YEATS4表达降低(P<0.05)。结论 Ac-SDKP可能通过抑制YEATS4发挥抗矽肺纤维化的作用。Objective To investigate the anti-effects of N-acetyl-seranyl-aspartate-lysyl-proline(Ac-SDKP)on experimental silicosis by regulating YEATS domain-containing protein 4(YEATS4).Methods RAW264.7 cells were divided into a si RNA-negative control(NC)group(siC),si RNA-YEATS4 group(siY),silicon dioxide(SiO_(2))+si RNANC group(S+siC),and SiO_(2)+si RNA-YEATS4 group(S+siY).In addition,there was a control group(C),SiO_(2)-induced group(S),SiO_(2)+Ac-SDKP treatment group(S+Ac),and AC-SDKP treatment group(Ac).Wistar rats were randomly divided into a control 24-week group(C24),silicosis 24-week group(S24),and Ac-SDKP treatment 24-week group(Ac24).Expression of collagen type I(COL I),monocyte chemoattractant protein-1(MCP-1),arginase 1,and YEATS4 were measured by western blotting in lung tissue and RAW264.7 cells.Immunohistochemical staining was used to detect YEATS4 expression and localization in lung tissue and RAW264.7 cells.Results Western blot showed downregulated protein expression levels of COL I,MCP-1,and arginase 1 in the siY and S+si Y groups compared with the siC and S+siC groups(P<0.05).Compared with the C group,the levels of COL I,MCP-1,arginase,and YEATS4 were increased in the S group.In addition,the levels of COL I,MCP-1,arginase 1,and YEATS4 were reduced in the S+Ac group compared with the Sgroup in RAW264.7 cells(P<0.05).Immunohistochemistry and Western blot showed that expression of COL I,MCP-1,arginase-1,and YEATS4 was up-regulated in the S24 group compared with the C24 group.Expression of COL I,MCP-1,arginase-1,and YEATS4 in the Ac24 group was decreased compared with S24 silicosis rats(P<0.05).Conclusions Ac-SDKP may play a suppressing role in silicosis by inhibiting YEATS4.

关 键 词：矽肺纤维化 含YEATS结构域蛋白4 RAW264.7细胞 N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酰 

分 类 号：R-33[医药卫生]