亚毒性剂量毒死蜱降低新西兰兔ABCA1表达加重高脂诱导的动脉粥样硬化  

Subtoxicdose of Chlorpyrifos Down Regulates ABCA1 Expression and Accelerates Formation of Atherosclerosis Induced by The High Fat Diet in New Zealand Rabbits

作　　者：周寿红[1,2] 杨旭红[2] 宋涛[2] 吴树金[2,3] 黄宁江[2,4] 刘立英[2] 

机构地区：[1]南华大学医学院生理学教研室,衡阳421001 [2]中南大学药学院药理学教研室,长沙410078 [3]长沙医学院药理教研室,长沙4102194 [4]永州职业技术学院药理学教研室,永州425000

出　　处：《生物化学与生物物理进展》2011年第1期46-54,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30570754);湖南省教育厅科学基金资助项目(08C746)~~

摘　　要：为了探讨亚毒性剂量有机磷酸酯杀虫剂毒死蜱对高脂饮食诱导的动脉粥样硬化的影响及其机制,32只健康雄性新西兰兔随机分为对照组、毒死蜱组、高脂组、高脂+毒死蜱组.每天以20 mg/kg亚毒性剂量的毒死蜱灌胃处理6个月.动物处死后检测血脂水平和血清胆碱酯酶活性.收集腹腔巨噬细胞,测定其胆固醇流出率.苏丹Ⅳ染色观察胸主动脉粥样硬化斑块,定量分析动脉粥样硬化斑块占血管内表面积的百分比.颈总动脉石蜡切片,观察动脉粥样硬化斑块.采用实时定量PCR和蛋白质印迹检测,分别检测肝脏、血管和腹腔巨噬细胞中三磷酸腺苷结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)mRNA和蛋白质的表达.结果显示:与对照组相比,高脂饮食升高了血清总胆固醇和脂蛋白水平,主动脉和颈总动脉出现明显的动脉粥样硬化斑块,其肝脏、主动脉和腹腔巨噬细胞ABCA1的表达升高,腹腔巨噬细胞中胆固醇流出增加;与对照组相比,毒死蜱组血清胆碱酯酶活性降低,但没有出现明显的中毒症状和肝肾功能损伤,血清中高密度脂蛋白(HDL)水平降低,ABCA1的表达降低,腹腔巨噬细胞中胆固醇流出减少;高脂+毒死蜱组与高脂组相比,血清胆碱酯酶活性降低,也没有出现明显的中毒症状和肝肾功能损伤,ABCA1的表达降低,腹腔巨噬细胞中胆固醇流出减少,主动脉和颈总动脉粥样硬化斑块更加明显.结果提示长期暴露于亚毒性剂量的毒死蜱可加速高脂饮食的致动脉粥样硬化作用,其机制可能与毒死蜱降低体内ABCA1的表达和胆固醇流出有关.In order to explore the effect of exposure to subtoxic dose of organophosphorus insecticide chlorpyrifos on the formation of atherosclerosis induced by the high fat diet in New Zealand rabbits and analyze the possible mechanisms,thirty two healthy male New Zealand rabbits were divided randomly into four groups： control,high-fat diet,chlorpyrifos and high-fat diet ＋ chlorpyrifos group.Subtoxic dose of chlorpyrifos（20 mg/kg·d） was administered by lavage every day for six months.The levels of serum fat,activities of cholinesterase and alanine aminotransferase,serum creatinine and blood urea nitrogen were measured respectively.The peritoneal macrophages were assembled and cellular cholesterol efflux was analyzed.Area of atherosclerosis plaque of thoracic aorta was measured by Sudan Ⅳ.Common carotid artery was fixed in formalin,sliced and HE dyed and pathology analysis system was used.The expression of ABCA1 was detected by Real-time PCR and Western blot.Compared with control group,serum TC,LDL and TG were singificantly increased and expressions of ABCA1 in liver,aorta and peritoneal macrophages were markedly increased and cholesterol efflux of peritoneal macrophages was significantly increased in high-fat diet group.There was obvious atherosclerosis lesion in thoracic aorta and common carotid artery in high-fat diet group.Compared with control group,activity of cholinesterase was singificantly decreased,but there were no symptom of intoxation and injury of function of liver and kidney,and level of HDL,expression of ABCA1 and cholesterol efflux were markedly decreased in chlorpyrifos group.Compared with high-fat diet group,activity of cholinesterase was decreased,but there were no symptom of intoxation and injury of function of liver and kidney,and expression of ABCA1 and cholesterol efflux were singificantly decreased,the atherosclerosis lesion areas in thoracic aorta and common carotid artery were increased in high-fat diet ＋ chlorpyrifos group.These results suggest that a long time exposure to subtoxic

关 键 词：毒死蜱 三磷酸腺苷结合盒转运体1 胆固醇流出 动脉粥样硬化 

分 类 号：R363[医药卫生—病理学]