AcSDKP对大鼠矽肺c-jun氨基末端激酶通路活化的调节作用  

Regulating effect of N-acetyl-seryl-aspartyl-lysyl-proline on activation of c-jun N-terminal kinase pathway in rats with silicosis

作　　者：魏中秋[1,2] 于婉莹 冯海利 马文东 李治国 徐洪 王瑞敏 杨方[1,2] 

机构地区：[1]河北联合大学病理学教研室,河北唐山063000 [2]医学实验研究中心 [3]武安市第一人民医院病理科

出　　处：《中华劳动卫生职业病杂志》2013年第5期335-340,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金项目（81072254）;河北省自然科学基金（C2011401024）;中华人民共和国人事部留学人员科技活动基金（国人厅发[2006]164号）;河北联合大学科学研究基金项目（z201228）

摘　　要：目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对c-jun氨基末端激酶（JNK）信号转导通路活化的调节在矽肺纤维化中的作用。方法选用非暴露式气管灌注法制作大鼠矽肺模型。60只大鼠随机分为对照4周组、对照8周组、矽肺模型4周组、矽肺模型8周组、AcSDKP治疗组、AcSDKP预防组，每组10只。采用对二甲氨基苯甲醛显色法检测肺组织中羟脯氨酸含量，免疫印迹法检测肺组织内转化生长因子（TGF）-β、磷酸化-JNK、JNK、c-jun蛋白的表达。培养新生大鼠肺成纤维细胞，第4代细胞用于实验，分为对照组、TGF-β1刺激组、SP600125干预组、AcSDKP干预组。免疫细胞化学法检测磷酸化．JNK和c-jun蛋白的分布，免疫印迹法检测I型、Ⅲ型胶原表达。结果AcSDKP治疗组大鼠肺组织中TGF-β1、磷酸化-JNK、c-jun蛋白表达和羟脯氨酸含量分别是矽肺模型4周组的70．60％、78．03％、79．85％和71．28％，分别是矽肺模型8周组的77．99％、66．73％、69．94％和64．82％；AcSDKP预防组大鼠肺组织中TGF-β1、磷酸化-JNK、c-jun蛋白表达和羟脯氨酸含量分别为矽肺模型8周组的84．56％、61．18％、64．73％和74．96％，差异均有统计学意义（P〈0．05）。AcSDKP干预组大鼠肺成纤维细胞磷酸化-JNK和c-jun蛋白的表达分别是TGF-β1刺激组的54．59％和55．56％，AcSDKP干预组大鼠肺成纤维细胞I型和Ⅲ型胶原蛋白的表达分别是TGF-β1刺激组的79．9％和84．4％，差异均有统计学意义（P〈0．05）。结论AcSDKP可能通过阻制TGF-β1介导的JNK信号转导通路的活化，抑制间质胶原的沉积，进而发挥其抗矽肺纤维化的作用。Objective To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline （AeSDKP） on the activation of e-inn N-terminal kinase （JNK） signal transduction pathway and its role in silicotic fibrosis. Methods A rat model of silicosis was developed by intratracheal instillation. Sixty rats were randomly divided into 4-week control group （n=10）, 8-week control group （n=10）, 4-week silicosis model group （n=10）, 8-week silicosis model group （n=10）, AcSDKP treatment group （n=10）, and AcSDKP prevention group （n=10）. The content of hydroxyproline in lung tissue was measured using a p-dimethylaminobenzaldehyde reagent; the expression levels of transforming growth factor （TGF）-beta 1 （TGF-β1）, phospho-JNK, JNK, and c-jun in lung tissue were measured by Western blot. The lung fibroblasts from neonatal rats were cul- tured, and the 4th generation of cells were used in the experiment; these cells were divided into control group, TGF-131 stimulation group, SP600125 intervention group, and AcSDKP intervention group. The distributions of phospho-JNK and e-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type I collagen and type III collagen in lung fibroblasts were measured by Western blot. Results The expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AeSDKP treatment group were 70.60%, 78.03%, 79.85%, and 71.28%, respectively, of those in the 4-week silicosis model group （P〈 0.05） and 77.99%, 66.73%, 69.94%, and 64.82%, respectively, of those in the 8-week silicosis model group （P〈0.05）; the expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56%, 61.18%, 64.73%, and 74.96%, respectively, of those in the 8-week silicosis model group （P〈0.05）. The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59% and 55.56%, respectively, of those in the TGF-β1 stimulation group; the

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 矽肺 羟脯氨酸 胶原 

分 类 号：R563.9[医药卫生—呼吸系统]