磷酸三邻甲苯酯对母鸡中枢神经组织线粒体中ATP含量及ATPase的影响  

Effects of tri-ortho-cresyl phosphate on mitochondrial ATP level and ATPase in hens' central nervous tissues

作　　者：辛星[1] 陈晶晶[1] 钟志霞[1] 曾涛[1] 张翠丽[1] 谢克勤[1] 赵秀兰[1] 

机构地区：[1]山东大学公共卫生学院毒理学研究所,山东济南250012

出　　处：《毒理学杂志》2010年第6期428-432,共5页Journal of Toxicology

基　　金：国家科技部973课题(2002CB512907);山东省自然科学基金(Y2007C019)

摘　　要：目的观察磷酸三邻甲苯酯(tri-ortho-cresyl phosphate,TOCP)对母鸡中枢神经组织线粒体ATP含量及ATP合成酶(ATP synthase,ATPase)的影响,探讨有机磷化合物诱导迟发性神经毒性(organophosphorus ester-induceddelayed neurotoxicity,OPIDN)的机制。方法成年罗曼母鸡96只随机分为实验组和对照组。实验组分别按185、375和750 mg/kg经灌胃一次性染毒TOCP,对照组给予等体积玉米油。分别于染毒1、5、15和21 d处死动物,迅速剥离大脑和脊髓,分离提纯其线粒体,生物发光法检测线粒体ATP含量的改变,并分别采用RT-PCR和Western blotting技术检测了ATPase mRNA水平及蛋白水平的改变。结果实验组与对照组相比,母鸡大脑中线粒体ATP含量没有明显改变,脊髓中3个剂量组均从第5天开始即出现明显降低,第21天线粒体ATP含量较第15天有所升高。RT-PCR结果表明,TOCP染毒后母鸡中枢神经组织中ATPase 6 mRNA水平与正常对照组相比均明显降低。Western blotting结果显示大脑和脊髓中均呈现先升高后降低的趋势,脊髓ATPaseβ蛋白含量变化比大脑变化更明显。结论 TOCP能使母鸡中枢神经组织线粒体ATP含量发生改变,并能引起ATPase mRNA水平和蛋白水平的改变。Objective To study the effects of Tri-ortho-cresyl phosphate（TOCP） on concentrations of mitochondrial ATP,levels of ATPase mRNA and protein in hen’s central nervous tissues and investigate the mechanism of the organophospho-rus ester-induced delayed neurotoxity（OPIDN）.Method 96 adult Roman hens were randomly divided into four groups： three treated groups and one control group（n = 24 each group）.The hens in three treated groups were given TOCP at dosages of 185,375 and 750 mg/kg,respectively,and control hens were treated with equivalent volume of corn oil via oral gavage.At day 1,5,15 and 21 of treatment,hens were sacrificed and the cerebrum and spinal cord were dissected.The mitochondrion in these nerve tissues were extracted to determine the changes of ATP concentration and the alterations of ATPase mRNA level and protein level.Results There was no significant difference in ATP concentration of hens’cerebral mitochondrion between TOCP treated groups and control group.In spinal cord,the ATP concentration decreased significantly from day 5 post-dosing.At day 21 post-dosing the ATP concentration was a little increased compared with day 15.The RT-PCR results showed ATPase 6 mRNA levels in TOCP treated hens’central nervous tissues were significantly declined when compared with control group.Western blotting results indi-cated the ATPase β protein levels in both cerebrum and spinal cord were increased at first and then decreased.The changes in spinal cord were more obvious than those in cerebrum.Conclusion TOCP could lead to alterations of mitochondrial ATP con-centration in hens’central nervous tissues and disturb the gene and protein expression of ATPase in mitochondrial respiratory chain,which might be one of the mechanisms of OPIDN development.

关 键 词：磷酸三邻甲苯酯 有机磷化合物诱发的迟发性神经毒性 ATP合成酶 

分 类 号：R114[医药卫生—卫生毒理学]