敌百虫加重高脂饮食致兔动脉粥样硬化作用与降低对氧磷酶活性有关  

Effect of Organophosphorus Insecticide to Aggravate Hyperlipidemic Diet Inducing Atherosclerosis Ralated to Decrease of Paraoxonase Activity in Rabbits

作　　者：熊小明[1] 周寿红[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,湖南省长沙市410078

出　　处：《中国动脉硬化杂志》2009年第3期172-176,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(30570754)

摘　　要：目的为了探讨慢性口服有机磷酸酯类农药敌百虫能否导致动脉粥样硬化的发生及其机制。方法32只健康新西兰兔随机分为正常饲料组、正常饲料+敌百虫18mg/(kg.d)组、正常饲料+高脂饲料组、正常饲料+高脂饲料+敌百虫组。动物单笼饲养70d。处死后进行离体血管功能、生化参数及病理组织学分析以及血液生化参数的分析。结果兔口服敌百虫70d,其血清对氧磷酶和胆碱酯酶及超氧化物歧化酶活性降低;丙二醛含量升高;血管内皮依赖性舒张反应降低。高脂饮食除导致与敌百虫相似的参数改变外,尚有血浆总胆固醇和脂蛋白的升高及血管壁具有动脉粥样硬化特征的病理形态学改变。敌百虫单独导致了血管内功能的皮损伤、血浆一氧化氮浓度降低和诱发了氧化应激反应,加重了高脂饮食的致动脉粥样硬化作用。结论长期慢性口服敌百虫可加重高脂饮食的致动脉粥样硬化作用,其机制可能与敌百虫降低体内对氧磷酶活性和触发机体的氧化应激反应有关。Aim It was presumed that Chronic orally organophosphorus insecticide may consume PON1 and result in development of atheroselerosis. The aim of the present study was to explore whether chronic orally organophosphorus insecticide trichlorfon has a similar or aggravating atherogenic effect of hyperlipidic diet and analyze the possible mechanisms. Methods 32 healthy male New Zealand rabbits were divided randomly into 4 groups with 8 rabbits in each group. They were fed a standard normal chow, normal chow plus trichlorfon 18 mg/（ kg · d ） , the hyperlipidic （ 50 g/d ） chow which containing 1% cholesterol and 7.5% yolk powder and 8% lard and trichlorfon plus hyperlipidie chow respectively. After 70 days, rabbites were sacrificed, the function, parameters of both biochemistry and pathohistology in isolated vesseles and blood were analyzed. Results The treatment of triehloffon and hyperlipidic diet resulted in a significant inhibition of the ACh-indueed endothelium-dependent relaxation response, but did not in sodium nitroprusside induced endothelium-independent relaxation in isolated aortic rings from rabbits, a significant decrease of activity of both paraoxonase and superoxide dismutase and a significant increase of concentration of malondialdehyde in sera. An activity of cholinesterase was markedly decreased in the alone trichlorfon treated group, but was significantly increased in hyperlipidic diet group. Hyperlipidic diet resulted in pathologic changes of atherosclerosis examined by light microscopy including that the vascular intima become more rough and thicker than normal, a lot of lipid foam cells migrated to regions under intima interval and smooth muscle cells were arranged in more disorder than normal group, triehlorfon alone did not, but aggravated significantly those changes induced by hyperlipidic diet. Conclusion A long time orally trichlorfon could result in injuries of vascular endothelial function and accelerate atherogenic effects of hyperlipidie diet. The mechanism may be related to the dec

关 键 词：敌百虫 兔 动脉粥样硬化 对氧磷酶 血管内皮依赖性舒张反应 

分 类 号：R363[医药卫生—病理学]