TGF-β1/ERK5信号通路对大鼠矽肺纤维化的影响  

Effect of TGF-β1/ERK5 signaling pathway on silicosis fibrosis in rats

作　　者：郝雪洁 陈赫 周效宝[3] 张步云 张安然 王瑞[1] 张海东[1] HAO Xuejie;CHEN He;ZHOU Xiaobao;ZHANG Buyun;ZHANG Anran;WANG Rui;ZHANG Haidong(Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong 250062,China;Qingdao Fuwai Cardiovascular Hospital,Qingdao,Shandong 266034,China;Jining Psychiatric Hospital&Jining Occupational Disease Hospital,Jining,Shandong 272051,China;College of Basic Medicine&Institute of Basic Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong 250062,China)

机构地区：[1]山东省职业卫生与职业病防治研究院,山东第一医科大学(山东省医学科学院),山东济南250062 [2]青岛阜外心血管病医院,山东青岛266034 [3]济宁市精神病防治院(济宁市职业病医院),山东济宁272051 [4]山东第一医科大学(山东省医学科学院)基础医学院(基础医学研究所),山东济南250062

出　　处：《环境与职业医学》2021年第4期414-418,共5页Journal of Environmental and Occupational Medicine

基　　金：山东省重点研发计划项目(2017GSF18143,2017GSF218042);山东省医药卫生科技发展计划项目(2015WS0169)。

摘　　要：[背景]矽肺发病机制尚不清楚,探讨矽肺纤维化的机制可以为矽肺纤维化的治疗提供指标。[目的]探讨转化生长因子-β1(TGF-β1)/细胞外信号调节激酶5(ERK5)信号通路在肺纤维化中的作用。[方法]选取SPF级Wistar健康雄性大鼠21只随机分为对照组、模型组和干预组,每组7只。模型组和干预组采用一次性非暴露气管染尘法建造大鼠急性矽尘暴露模型,造模完成24 h后,干预组大鼠腹腔注射Disitertide溶液0.8 mL(1 mg Disitertide粉末溶解于1 mL DMSO和9 mL生理盐水混合液中),模型组大鼠腹腔注射同比例溶剂0.8 m L(1 mL DMSO混合于9 mL生理盐水中),每3 d注射一次。染尘28 d后麻醉处死大鼠,取大鼠左上叶肺组织做石蜡包埋切片行HE染色、Masson染色;取右肺下叶经Western blotting法检测肺组织中有丝分裂原活化蛋白激酶激酶激酶2(MEKK2)、丝分裂原活化蛋白激酶激酶激酶3(MEKK3)、磷酸化丝裂原活化蛋白激酶激酶5(P-MEK5)、磷酸化细胞外信号调节激酶5(P-ERK5)蛋白水平;采用ELISA法检测血清中TGF-β1水平。[结果]与对照组相比,模型组大鼠肺脏器病理变化明显加重;与模型组相比,干预组大鼠肺脏器变化病理变化减轻。Western blotting法检测结果显示:与对照组相比,模型组和干预组大鼠MEKK2、MEKK3、P-MEK5、P-ERK5蛋白表达升高(P<0.05);与模型组相比,干预组MEKK2、MEKK3、P-MEK5、P-ERK5蛋白表达降低(P<0.05)。ELISA法检测结果显示:与对照组相比,模型组和干预组大鼠TGF-β1含量升高(P<0.05);与模型组相比,干预组大鼠TGF-β1含量降低(P<0.05)。[结论]抑制TGF-β1/ERK5信号通路可以降低TGF-β1及其下游MEKK2、MEKK3、P-MEK5、P-ERK5蛋白的表达,从而抑制大鼠矽肺纤维化。[Background]The pathogenesis of silicosis is not clarified.To explore its pathogenesis can provide indicators for the treatment of silicosis fibrosis.[Objective]This experiment investigates the role of transforming growth factor-β1(TGF-β1)/excellular signal-regulated kinase 5(ERK5)signaling pathway in pulmonary fibrosis.[Methods]Healthy male Wistar rats of SPF grade(n=21)were randomly divided into a control group,a model group,and an intervention group,7 rats per group.The model group and the intervention group were treated with one-time non-exposure method to establish an acute silica exposure model.After 24 h,the rats in the intervention group were intraperitoneally injected with 0.8 mL of Disitertide solution(1 mg Disitertide powder dissolved in 1 mL DMSO and 9 mL normal saline),and the rats in the model group were intraperitoneally injected with 0.8 mL of solvent(1 mL DMSO and 9 mL normal saline),once every 3 d.After the rats were anesthetized,the left upper lobe tissue samples were paraffin-embedded,sliced,and stained with HE and Masson;the right lower lobe tissues were sampled to detect the protein levels of mitogen-activated protein kinase kinase kinase 2(MEKK2),mitogen-activated protein kinase kinase kinase 3(MEKK3),phospho-mitogen activated protein kinase kinase 5(P-MEK5),and phospho-excellular signal-regulated kinase 5(P-ERK5)by Western blotting;the level of TGF-β1 in serum was detected by ELISA.[Results]Compared with the control group,the pathological changes of lungs in the model group and the intervention group were significantly aggravated,and the pathological changes in the intervention group were reduced compared with the model group.The results of Western blotting showed that compared with the control group,the expression levels of MEKK2,MEKK3,P-MEK5,and P-ERK5 in the model group and the intervention group were significantly increased(P<0.05);but compared with the model group,the expression levels of the four indicators in the intervention group were significantly decreased(P<0.05).The results

关 键 词：肺纤维化 转化生长因子-Β1 细胞外信号调节激酶5 抑制 

分 类 号：R114[医药卫生—卫生毒理学]