乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响  

Tolerance of Rats and Modification of M-receptors in Rat Brains Induced by Sub-acute Administration of Dimethoate

作　　者：孙运光[1] 周志俊[1] 胡云平[1] 陈嘉[1] 金泰廙[1] 

机构地区：[1]复旦大学公共卫生学院,上海200032

出　　处：《环境与职业医学》2003年第3期154-158,共5页Journal of Environmental and Occupational Medicine

基　　金：教育部博士点基金 (2 0 0 0 4 0 );复旦大学公共卫生学院与上海市疾病预防控制中心联合基金

摘　　要：[目的 ]通过连续低剂量乐果染毒 ,建立大鼠对乐果的耐受模型 ,然后再用高剂量乐果激发染毒 ,观察激发染毒后大鼠全血胆碱酯酶和脑组织中M受体的变化 ,以了解耐受的生理病理意义。 [方法 ]将大鼠随机分为对照组及 3个染毒组。首先对各染毒组连续 14d皮下注射 2 5mg/kg乐果 ,然后将染毒动物分别给以生理盐水、5 0mg/kg、10 0mg/kg乐果激发。实验过程中系统记录动物的中毒症状 ,采集尾静脉血检测胆碱酯酶活性。激发 2 4h后 ,处死动物 ,取脑组织测定胆碱酯酶活性和M受体M1、M2 亚型密度、亲和力 ,并作电镜检查。 [结果 ]低剂量诱导染毒后 ,全血胆碱酯酶活性持续下降 ,到第 12天时接近最低值 ,激发染毒后 ,大鼠全血胆碱酯酶活性下降不明显 ,生理盐水激发组全血胆碱酯酶活性有一定恢复。不同剂量激发的动物脑组织中M1、M2 受体的密度和亲和力差别经检验仅M1受体密度下降有统计学意义。脑组织电镜检查发现高剂量激发组动物有典型神经元坏死。 [结论 ]耐受动物可以抵抗更高剂量的乐果染毒而不出现明显的有机磷急性中毒症状 ,说明耐受动物有了保护能力。但是电镜下观察到脑神经元的典型坏死 ,提示耐受可能存在潜在的健康危害。Objective] This study is to observe the physiological and/or pathological effect of tolerance induced by sub acute administration of dimethoate in rats. [Methods] 24 Sprague Dawley rats were divided into 4 groups randomly. Three groups of rats were given 25 mg/kg dimethoate daily while the control group was given saline daily instead for 14 days. The activity of whole blood acetylcholinesterase was measured at different times by collecting tail vein blood. Three groups of administrated rats were challenged by saline solution,50 mg/kg or 100 mg/kg of dimethoate,respectively on 15 th day. The rats were sacrificed and the brains were removed. The density and affinity of brain M 1,M 2 receptors were determined by radioligand binding assay. The acetylcholinesterase activity was measured by colorimetric assay with ASCh DTNB. [Results] The activity of whole blood cholinesterase decreased consistently during the inducing period and reached the lowest value on 13 th day. When rats were challenged by higher doses of dimethoate,cholinesterase level didnt decrease significantly while the acetylcholinesterase of rats without challenge recovered to some extent. There were no statistical differences of density and affinitiy of brain M 2 receptors among the four groups,while only density of M 1 receptors showed statistical differences . Typical necrosis of neurons in the brains was observed in the rats with the highest dose challenge under the electronic microscope . [Conclusion] Rats tolerant of dimethoate could resist the adverse effects of higher dose of dimethoate and manifest no obviously typical symptoms. This indicated that tolerance is of protective effect,but the finding of neuron necrosis under electron microscope examination may suggest the potentially adverse effects also exist.

关 键 词：乐果 亚急性染毒 大鼠 耐受 脑组织 M受体 胆碱能受体 低剂量 有机磷农药 

分 类 号：R99[医药卫生—毒理学] R139.3[医药卫生—药学]