嘌呤核苷酸补偿对海洛因依赖大鼠痛阈影响.docVIP

嘌呤核苷酸补偿对海洛因依赖大鼠痛阈影响 　 作者：李鸿梅 李昆 何海涛 刘剑凯 洪敏 【摘要】 目的 探讨嘌呤核苷酸补偿对海洛因依赖大鼠痛阈的影响。方法 将50只雄性Wistar大鼠随机分为对照组、海洛因组和海洛因+AMP+GMP组、海洛因+AMP组、海洛因+GMP组。于实验1、3、5、7 d用电子压痛仪检测大鼠尾压痛阈值,2、4、6、8 d进行热甩尾实验检测大鼠抗热痛觉过敏能力。结果 与对照组相比,第1天海洛因组及海洛因补偿嘌呤核苷酸组压痛阈值有所增加，但差异不显著(Pgt;0.05);第3天起海洛因+嘌呤核苷酸组压痛阈值明显高于海洛因组(Plt;0.05)。第2天起海洛因组热甩尾潜伏期延长(Plt;0.05);第4天起海洛因+嘌呤核苷酸组热甩尾潜伏期时间长于海洛因组(Plt;0.05)。结论 嘌呤核苷酸补偿能够明显增强海洛因的镇痛作用。 【关键词】 嘌呤核苷酸;海洛因;痛阈 　　【Abstract】 Objective To investigate the effects of purine nucleotides compensation on pain threshold in heroin dependent rats. Methods 50 male Wistar rats were randomly divided into control (C), heroin (H), heroin plus purine nucleotides (Heroin +AMP+GMP, AMP and GMA were mixed in equimolar, HAG), heroin plus AMP (Heroin+AMP, HA) and heroin plus GMP groups (Heroin+GMP, HG). Rat′s tail pressurepain threshold was detected at 1, 3, 5 and 7 d by electric pressure pain instrument. Rat antithermopain ability was examined at 2, 4, 6, and 8 d by tail flick test. Results The pressurepain threshold on rats tail was increased in H and HAG groups from 1 d comparing to that of C group, but the difference was not significant (Pgt;0.05); the threshold of HAG group was higher than that of H group from 3 d (Plt;0.05). The latency of tail flick was increased in H group from 2 d (Plt;0.05), and the latency was higher in HAG group than that in H group from 6 day (Plt;0.05). Conclusions Purine nucletogides compensation can increase the analgesic effect of heroin in heroin dependent rats. 　　【Key words】 Purine nucleotides; Heroin; Pain threshold 　 嘌呤核苷酸是核苷酸的组成成分,分为腺嘌呤核苷酸(AMP)和鸟嘌呤核苷酸(GMP)，在体内可去磷酸化生成腺苷和鸟苷。存在于细胞间的嘌呤核苷酸及嘌呤核苷主要通过与其受体相互作用产生效应〔1〕。有研究表明腺苷A1受体激动剂在临床上作为镇痛剂应用〔2〕，能够明显减轻病理性疼痛〔3〕。Lao等〔4〕也发现腺苷能够激活A1受体而抑制疼痛反应。腺苷受体和阿片受体在生理和病理状态下均有密切的联系〔5〕。海洛因是典型的阿片受体激动剂,作用于中枢神经系统可产生明显的镇痛、镇静作用,可抑制病人因紧张、烦躁、焦虑等精神因素引起的痛觉过敏及躯体不适症状,但会引起躯体依赖和精神依赖,撤药后有严重的不适症状及对药物强烈的渴求。本实验室前期研究发现，长期应用吗啡、海洛因等阿片类物质可引起嘌呤核苷酸分解过度 〔6～9〕，表明在阿片依赖的大鼠脑内可能存在嘌呤核苷酸匮乏，并且嘌呤核苷酸能够增强吗啡依赖大鼠的痛阈〔10〕。因此，本实验在前期研究结果的基础上，重点研究嘌呤核苷酸对海洛因镇痛效应的影响。 　　1 材料与方法 　　1.1 材料