N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸调节α-微管蛋白乙酰转移酶1抑制矽肺纤维化  

Inhibition effect of Ac-SDKP on silicotic fibrosis via regulating α-TAT1

作　　者：张巧丹 牛思宇 李耕旭 陈建星 汤庆南 徐洪 杨方 耿玉聪 李世峰 ZHANG Qiaodan;NIU Siyu;LI Gengxu;CHEN Jianxing;TANG Qingnan;XU Hong;YANG Fang;GENG Yucong;LI Shifeng(Medical Experiment Research Center,North China University of Science and Technology,Tangshan 063210,China;不详)

机构地区：[1]华北理工大学医学实验研究中心,河北唐山063210 [2]华北理工大学基础医学院,河北唐山063210

出　　处：《实用医学杂志》2019年第23期3597-3601,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金项目（编号：81472953）;河北省自然科学基金项目（编号：H2016209170）;华北理工大学大学生创新项目（编号：X2018359）

摘　　要：目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(Ac-SDKP)能否通过对α-微管蛋白乙酰转移酶1(α-TAT1)调节而发挥抗矽肺纤维化作用。方法Wistar大鼠随机分为3组:对照组、矽肺模型组、Ac-SDKP处理组,每组6只。原代培养大鼠的肺成纤维细胞分为5组:对照组、转化生长因子(TGF-β1)诱导组、Ac-SDKP预处理组(TGF-β1+Ac-SDKP)、α-TAT1沉默组(α-TAT1-siRNA+TGF-β1+Ac-SDKP)、α-TAT1过表达组(α-TAT1-cpDNA+TGF-β1+Ac-SDKP)。免疫组化检测大鼠肺组织中α-TAT1的表达与分布,Western blot检测大鼠肺组织及大鼠肺成纤维细胞中I型胶原(Col I)、α-平滑肌肌动蛋白(α-SMA)、乙酰化微管蛋白-α(Ac-Tubα)、α-TAT1蛋白的表达水平。结果矽肺模型组大鼠的肺组织中出现矽结节,α-TAT1在矽结节中表达缺失,Western blot结果显示,矽肺模型组和TGF-β1诱导的肺成纤维细胞中Col I和α-SMA蛋白表达上调,Ac-Tubα和α-TAT1蛋白表达下调。Ac-SDKP治疗可抑制该变化。Ac-SDKP对Col I、α-SMA表达抑制效应可被α-TAT1-siRNA阻断,而α-TAT1过表达可加强Ac-SDKP对Col I、α-SMA表达的抑制作用。结论Ac-SDKP通过调节α-TAT1的表达抑制肌成纤维细胞分化,发挥抑制矽肺大鼠肺纤维化的作用。Objective To investigate the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline(AcSDKP)on silicosis fibrosis through regulatingαtubulin acetyltransferase 1(α-TAT1).Methods Wistar rats were randomly divided into 3 groups:model control group,silicotic model group and Ac-SDKP pre-treatment group(n=6).Primary lung fibroblasts of rats were divided into 5 groups:(1)control group,(2)Transforming growth factor-β1(TGF-β1)induced group,(3)Ac-SDKP treatment group(TGF-β1+Ac-SDKP),(4)α-TAT1 silencing group(α-TAT1-siRNA+TGF-β1+Ac-SDKP),(5)α-TAT1 overexpression group(α-TAT1-cpDNA+TGF-β1+Ac-SDKP).The distribution and the expression ofα-TAT1 were examined by immunohistochemical staining.The expression of type I collagen(Col I),α-smooth muscle actin(α-SMA),acetylated tubulinα(Ac-Tubα)andα-TAT1 in lung tissue and lung fibroblasts were analyzed by Western blot assay.Results The expression ofα-TAT1 was undetectable in the silicotic nodules of silicosic model group.The expression of Col I andα-SMA were increased and the expression of Ac-Tubαandα-TAT1 were decreased in silicotic model group and fibroblast induced by TGF-β1,which were inhibited by Ac-SDKP.The effect of Ac-SDKP that mediated downregulation of Col I andα-SMAwas blocked byα-TAT1-siRNA.However,overexpression ofα-TAT1 could enhance the inhibition effect of Ac-SDKP on Col I andα-SMA(P<0.05).Conclusions Ac-SDKP is capable of restraining myofibroblast differentiation via activatingα-TAT1,so as to inhibit silicosis fibrosis.

关 键 词：矽肺 肺纤维化 N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 微管蛋白 α-微管蛋白乙酰转移酶1 大鼠 

分 类 号：R13[医药卫生—劳动卫生]