Ac-SDKP对胞内氯离子通道蛋白4抑制矽肺大鼠纤维化的调节作用  

Effect of Ac-SDKP on the expression of CLIC4 in the lungs of rats with silicosis

作　　者：郭地利 徐丁洁 李红垒 耿玉聪 高学敏 李世峰 徐洪 杨方 魏中秋 

机构地区：[1]华北理工大学医学实验研究中心,河北唐山063000 [2]华北理工大学中医学院中西医结合临床系,河北唐山063000

出　　处：《广东医学》2018年第2期171-175,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81472953);河北省自然科学基金资助项目(编号:H2016209107);河北联合大学科学研究基金项目(编号:z201228);华北理工大学大学生创新项目(编号:X2016211)

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)对肺成纤维细胞分化过程中胞内氯离子通道蛋白4(CLIC4)表达的影响。方法非暴露式支气管内灌注法制作大鼠矽肺模型,分为对照4周组、矽肺4周组、对照8周组、矽肺8周组、Ac-SDKP抗纤维化治疗组和Ac-SDKP预防治疗组,免疫组化法、Western blot法检测Ⅰ型胶原、α-平滑肌肌动蛋白(α-SMA)及CLIC4蛋白的表达。培养新生大鼠肺成纤维细胞,观察转化生长因子(TGF)-β1诱导肺成纤维细胞后Ⅰ型胶原、α-SMA、CLIC4蛋白表达变化,同时观察给予Ac-SDKP、Smad2/3特异性抑制剂LY364947、Rock-1特异性抑制剂Y-27632、ERK1/2特异性抑制剂PD98059、JNK特异性抑制剂SP600125和P38特异性抑制剂SB203580干预后对Ⅰ型胶原、α-SMA、CLIC4蛋白的影响。结果免疫组织化学染色结果显示矽肺大鼠矽结节内可见CLIC4阳性表达,给予Ac-SDKP抗纤维化治疗或预防治疗均能够抑制Ⅰ型胶原、α-SMA及CLIC4蛋白表达的上调。TGF-β1诱导肺成纤维细胞后CLIC4蛋白表达上调,而给予Ac-SDKP、LY364947、Y-27632或PD98059预处理均能够抑制该变化,SP600125和SB203580预处理后则无改变。结论 Ac-SDKP可能通过作用于TGF-β1介导的CLIC4激活途径,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 （ Ac - SDKP） on the expression of CLIC4 in the process of fibroblast differentiation. Methods Rats were instilled with silica through tra- chea to construct the silicosis model. The expression of α - SMA, collagen type ] and CLIC4 was measured by immuno- histochemistry and Western blot assay. Myofibroblasts induced by TGF - β1 were pre - treated with Ac - SDKP, LY364947, Y-27632, PD98059, SP600125 and SB203580. The expression of α- SMA, collagen type ] and CLIC4 was assessed by western blot. Results Compared with the corresponding control groups, the expression of α - SMA, col- lagen type I and CLIC4 was significantly increased in the lung tissues of the silicosis models. Compared with the corresponding model groups, after administration of Ac - SDKP, the expression of α - SMA, collagen type I and CLIC4 in the lung tissues was significantly reduced. In addition, Ac - SDKP, LY364947, Y - 27632 and PD98059 pretreatment effi- ciently ameliorated the up - regulation of CLIC4, myofibroblast differentiation and collagen deposition in fibroblasts induced by TGF - β1. Conclusion Ac - SDKP possibly plays an important role in anti - silieotic fibrosis by inhibiting the CLIC4 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 CLIC4 矽肺 纤维化 

分 类 号：R135.2[医药卫生—劳动卫生]