乐果对大鼠脑毒蕈碱受体的影响及其与胆碱酯酶的关系

目的　研究乐果急性染毒对大鼠脑M1、M2 受体的影响。方法　 2 4只SD大鼠随机分为 4组 ,采用皮下注射染毒 ,乐果剂量分别为 0、2 5、5 0、10 0mg/kg。染毒后 4 8h取大鼠脑组织 ,采用放射结合法分析M1、M2 受体数目和亲和力。结果　乐果各剂量染毒组大鼠胆碱能M1、M2 亚型的受体密度均低于对照组 ,其中 10 0mg/kg组大鼠脑中M1受体密度为 (2 4 4 .4± 81.4 )fmol/mgpro ,同对照组 [(44 0 .0± 95 .0 )fmol/mgpro]相比 ,差异有显著性 (P <0 .0 5 ) ,M2 受体密度与对照组的差异无显著性 (P >0 .0 5 )。染毒组大鼠脑M1、M2 受体亲和力均高于对照组 ,但差异无显著性 (P >0 .0 5 )。相关分析发现 ,脑组织中胆碱酯酶 (ChE)活力与M1受体密度相关 (r=0 .5 83,P <0 .0 1)。结论　急性乐果染毒后大鼠脑中M1、M2 受体密度有下降趋势 ,可能与ChE活力改变有关。提示机体胆碱能亢进症状减轻可能与大鼠脑中的M1、M2 受体数目的减少有关

The acute effects of dimethoate on the muscarinic-receptors of rat brains and the relationship between muscarinic-receptors and cholinesterase

Objective To study the acute effects of dimethoate on the muscarinic receptors(M 1?M 2) in the brain of rats. Methods 24 Sprague Dawley rats were divided into 4 groups randomly.They were administered subcutaneously with 0?25?50?100 mg/kg dimethoate,respectively.Brains were removed after 48 hours of administration.Radioligand binding assay was used to determine the density and affinity of M 1 and M 2 receptors. Results Rats in the treated group showed low density of M 1 and M 2 receptors compared with the control rats.The brain M 1 receptor density of the rats in the highest dosage group was significantly lower than that in the control group while brain M 2 receptors density had a decrease trend with increasing dosage,but the difference showed no significance.However,there were no differences of the affinity of both M 1 and M 2 among different treated groups.Correlation analysis showed there is positive relationship between cholinesterase activity and density of M 1 receptors(r= 0.583, P<0.01). Conclusion M 1 and M 2 receptors density decreased with the increasing dosage of dimethoate.It is suggested that the alleviating of cholinergic symptoms may be due to the decrease of M 1 and M 2 receptors in rat brain.