三邻甲苯磷酸酯染毒母鸡神经组织中自噬相关蛋白ATG4表达与磷酸化的变化  

Changes in the expression and phosphorylation state of autophagy-related protein ATG4 in nervous tissues of hens treated with tri-ortho-cresyl phosphate

作　　者：童彦菊 王沙沙[1] 王译苹 王富武[2] 谢克勤[1] 宋福永[1] 

机构地区：[1]山东大学公共卫生学院毒理学研究所,济南250012 [2]山东大学医学院组织学与胚胎学教研室,济南250012

出　　处：《中华劳动卫生职业病杂志》2015年第1期7-10,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金（81373043）;山东大学基本科研业务费资助项目（2014JC018）

摘　　要：目的 研究三邻甲苯磷酸酯（TOCP）染毒母鸡以及提前应用苯甲基磺酰氟（PMSF）后神经组织中自噬相关蛋白ATG4A与p-ATG4A表达的变化,探讨迟发性神经病（OPIDN）的发病机制.方法 选取成年罗曼母鸡60只,其中30只动物用于TOCP染毒实验,即动物随机分为对照组,1、5、10、21 dTOCP染毒组,剂量为600 mg/kg,一次性灌胃染毒.另外30只动物随机分为对照组,1、5、10、21 d PMSF干预组,提前24 h皮下注射90 mg/kg PMSF,然后再染毒600 mg/kg TOCP,用免疫印迹法检测胫神经ATG4A与p-ATG4A的相对含量.结果 与对照组比较,TOCP染毒后第1、5、10天胫神经ATG4A含量分别下降36％、43.7％,41％,染毒后第1、5、10天胫神经p-ATG4A含量分别下降22.5％、25％,21％差异有统计学意义（P＜0.05）.PMSF干预组动物胫神经中ATG4A 、p-ATG4A与对照组相比没有明显改变.结论 TOCP染毒后干扰了自噬相关蛋白ATG4A、p-ATG4A表达的变化,可能与OPIDN中神经元自噬活性变化有关.Objective To study the changes in the levels of authophagy-related proteins ATG4A and pATG4A in nervous tissue after treated with tri-ortho-cresyl phosphate and explore the possible pathogenesis of OPIDN.Methods In the first experiment,thirty hens were randomly divided into control group and 1 d,5 d,10 d and 21d treated groups,hens in treated groups were treated with TOCP by gavage at a single dosage of 600 mg/kg.In the second experiment,other thirty hens were also randomly divided into control group and 1 d,5 d,10 d and 21 d treated groups,hens in treated group were pretreated with PMSF by subcutaneous at a single dosage of 90 mg/kg.24 h later,hens in intervention group was treated with TOCP by gavage at a single dosage of 600 mg/kg.The hens were killed at the corresponding time points,and collected their tibial nerves.The levels of ATG4A and p-ATG4A were measured by immunoblotting.Results compared with the control group,the levels of ATG4A decreased by36% 、43.7% and 41% at 1 d、5d and 10d in the intoxication groups （P〈0.05）,the levels of p-ATG4A decreased by 22.5%,25% and 21% at 1d、5d and 10d in the intoxication group （P〈0.05）.However,compared with the control group,there is no significant change in the levels of ATG4A and p-ATG4A in PMSF-pretreated groups.Conclusion The intoxication of TOCP influence the levels of autophagy-related proteins ATG4A and p-ATG4A,which might be associated with the inhibition of autophagy activity in neurons of OPIDN.

关 键 词：三邻甲苯磷酸酯 苯甲基磺酰氟 自噬相关蛋白质类 

分 类 号：R114[医药卫生—卫生毒理学]