亚慢性亚毒性有机磷酯类杀虫剂抑制抗氧化酶而致兔血管内皮功能损伤(英文)  

Subchronic Toxicity Organophosphate Insecticideinduced Damages on Endothelial Function of Vessels in Rabbits by Inhibiting Antioxidases

作　　者：熊小明[1] 戴雯[1] 李鹏[1] 吴树金[1] 胡敏[1] 刘立英[1] 

机构地区：[1]中南大学药学院药理教研室,长沙410078

出　　处：《生物化学与生物物理进展》2010年第11期1232-1239,共8页Progress In Biochemistry and Biophysics

基　　金：supported by a grant from The National Natural Science Foundation of China(30570754)~~

摘　　要：有机磷酸酯类(OPs)是全球最广泛使用的杀虫剂之一.其除了抑制胆碱酯酶(AChE)活性外,也抑制对氧磷酶(PON1)的活性.其急性中毒主要与抑制AChE有关.最近,OPs对PON1的影响已引起学术界广泛关注.因为PON1除了有水解OPs的功能外,也有抗低密度脂蛋白(LDL)氧化和降解LDL中的脂质过氧化物的作用.因为血管内皮功能损伤是动脉粥样硬化形成的起始步骤.将探讨OPs对血管内皮功能的影响作为研究目的.研究结果表明,连续每天给兔灌胃敌百虫(18mg/kg)70天,可导致其离体血管内皮依赖性舒张(EDR)反应和eNOS活性显著性降低,血浆超氧化物岐化酶活性、一氧化氮水平、PON1和AChE活性降低,脂质过氧化代谢产物丙二醛水平增加.OPs的活性成分——对氧磷在体外与兔胸主动脉环直接孵育也能浓度和时间依赖性地显著抑制EDR.研究结果提示,亚慢性-亚毒性剂量的敌百虫灌胃或对氧磷与离体血管环直接孵育,均可导致兔血管内皮功能损伤,其机制可能与OPs抑制氧化酶和诱发氧化应激反应有关.Organophosphates are some the widely used pesticides in the world,their mechanism of acute toxicity is associated with inhibiting acetylcholinesterase（AChE） .Recently,increasing attention has been put to paraoxonase（PON1） which hydrolyzes OPs and prevents atherosclerosis by its anti-oxidation effects on low density lipoproteins（LDLs） ,resulted in decreased pro-inflammatory lipid peroxides formation.Since vascular endothelial dysfunction is known as the primary step in atherogenesis,the influence of OPs on the vascular endothelial function was assessed.Results showed that trichlorfon（18 mg·kg-1） intragastrically daily for 70 days in rabbits resulted in a significant inhibition of endothelium-dependent relaxation（EDR） ,a decrease of endothelium nitric oxide synthase（eNOS） activity in isolated aorta and the changes of biochemical parameters in plasma,including a decrease of superoxide dismutase（SOD） ,PON1 and AChE activity and nitric oxide level and an increase of malondialdehyde（MDA） level.In addition,a direct exposure of rabbit aortic rings to paraoxon also inhibited EDR.These findings suggest that subchronic toxicity dose intragastrically trichlorfon or vessels to be exposed directly to paraoxon in vitro could induce dysfunction of vascular endothelium.The mechanisms may involve an inhibition of antioxidases and oxidative stress induced by OPs.

关 键 词：敌百虫 兔 对氧磷酶 一氧化氮合酶 氧化应激 

分 类 号：R363[医药卫生—病理学]