三邻甲苯磷酸酯诱导母鸡神经组织中自噬相关蛋白含量的变化  

Changes in autophagy-related protein levels in nervous tissues of hens with tri-ortho.cresyl phosphate- induced delayed neuropathy

作　　者：邹朝双[1] 寇蕊蕊[1] 高媛[1] 谢克勤[1] 宋福永[1] 

机构地区：[1]山东大学毒理学研究所,济南250012

出　　处：《中华劳动卫生职业病杂志》2012年第10期748-750,共3页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金（30972498）和山东省中青年科学家科研奖励基金（BS2009SW017）

摘　　要：目的研究三邻甲苯磷酸酯（TOCP）诱导的迟发性神经病（OPIDN）中自噬相关蛋白Atg1、Atg5和Beclin1的变化，探讨OPIDN发生的分子机制。方法取成年罗曼母鸡30只，随机分为对照组、1d、5d、10d和21d组（每组6只），对照组给予同体积的玉米油，各染毒组动物均按750mg／kg经一次性灌胃染毒TOCP，分别在相应时间点处死动物取胫神经和脊髓，免疫印迹法检测胫神经和脊髓中Atg1、Atg5和Beclin1的相对含量。结果与对照组相比，TOCP染毒后胫神经中Atg1含量1、5、10、21d分别下降了29．8％、64．4％、43．5％和19．8％（P〈0．05）；TOCP染毒后Atg5含量1、5、10、21d分别下降了36．8％、49．6％、51．2％和31．5％（P〈0．05）；TOCP染毒后beclin1含量1、5、10天分别下降了68．5％、66．3％和32．2％（P〈0．05）。与对照组相比，TOCP染毒后脊髓组织中Atg1含量1、5、10d分别下降了23．5％、48．7％和20％（P〈0．05）；Atg5含量在TOCP染毒后1、5、10、21d分别下降了32．7％、51．5％、47．3％和39．6％（P〈0．05）；beclin1含量在TOCP染毒后1、5、10、21d分别下降了28．9％、50．2％、43．2％和28．3％（P〈0．05）。结论TOCP染毒干扰了母鸡神经组织中自噬相关蛋白的表达，可能与OPIDN的发病机制有关。Objective To study the changes in the levels of autophagy-related proteins, Atg1, Atg5, and Beclin1, in organophosphate-induced delayed neuropathy （OPIDN） caused by tri-ortho-cresyl phosphate （TOCP）, and to investigate the molecular pathogenic mechanism of OPIDN. Methods Thirty adult Roman hens were randomly and equally divided into control group and 1, 5, 10, and 21 d intoxication groups. Each hen in the intoxication group was administered TOCP by gavage at a single dose of 750 mg/kg, while each hen in the control group was administered the same volume of corn oil. The hens were killed at the corresponding time points, and their tibial nerves and spinal cords were collected. The levels of Atg1, Atg5, and Beclin1 in the tibial nerves and spinal cords were measured by immunoblotting. Results Compared with those in the control group, the levels of Atg1 in tibial nerves decreased by 29.8%, 64.4%, 43.5%, and 19.8% at 1, 5, 10, and 21 d, respectively, after intoxication （P〈0.05）; the levels of Atg5 in tibial nerves decreased by 36.8%, 49.6%, 51.2%, and 31.5% at 1, 5, 10, and 21 d, respectively, after intoxication （P〈0.05）; the levels of Beclin 1 in tibial nerves decreased by 68.5%, 66.3%, and 32.2% at 1, 5, and 10 d, respectively, after intoxication （P〈0.05）. Compared with those in the control group, the levels of Atg1 in spinal cords decreased by 23.5%, 48.7%, and 20% at 1, 5, and 10 d, respectively, after intoxication （P〈0.05）; the levels of Atg5 in spinal cords decreased by 32.7%, 51.5%, 47.3%, and 39.6% at 1, 5, 10, and 21 d, respectively, after intoxication （P〈0.05）; the levels of Beclin1 in spinal cords decreased by 28.9%, 50.2%, 43.2%, and 28.3% at 1, 5, 10, and 21 d, respectively, after intoxication （P〈0.05）. Conclusion The intoxication of TOCP is associated with the significant changes in the levels of autophagy- related proteins in the nervous tissues of hens, which might be involved in the pathogenesis of OPIDN.

关 键 词：三邻甲苯磷酸酯 有机磷化合物诱发的迟发性神经病 自噬相关蛋白 

分 类 号：R114[医药卫生—卫生毒理学]