摘要
目的:通过观察低频电针对实验性海洛因心理依赖小鼠海马组织内Ca~(2+)-CaM-CaMKⅡ细胞信号传导通路及磷酸化CREB的影响,探讨电针对海洛因成瘾记忆的干预作用可能性中枢机制,深入揭示针刺防复吸的作用机理。
方法:经CPP筛选后的48只昆明种小鼠,随机分为空白组、模型组、电针组。按剂量逐日递增的原则进行海洛因皮下注射,并结合CPP训练制作海洛因心理依赖模型,以低频电针“内关”、“三阴交”、点刺“四神聪”穴为治疗方法。采用行为学测试、RT—PCR和Western bloting等试验方法,观察电针对海马组织CaM、CaMKⅡa及p-CREB表达的影响。
结果:1、模型组小鼠在拌药盒停留时间较空白组明显延长(P＜0,01),电针组小鼠的停留时间明显较模型组缩短(P＜0.05)。2、模型组小鼠海马组织CaMmRNA、CaMKⅡa mRNA表达较空白组明显增高(P＜0.05),电针组则较模型组明显降低(P＜0.05);3、模型组小鼠海马组织CaMKⅡa和p—CREB的蛋白表达较空白组显著升高(P＜0.05),电针组则较模型组明显降低(P＜0.05)。
结论:电针对实验性海洛因心理依赖小鼠具有明显消退心理渴求的作用;电针对实验性海洛因心理依赖模型中与成瘾记忆相关的Ca~(2+)—CaM—CaMKⅡ信号通路及转录因子CREB具有下调的作用;电针可能通过影响成瘾记忆的巩固而达到防复吸的目的。
Objective:To study the effect of the Ca~(2+) signaling pathway and p-CREB in the hippocampus on experimental heroin psychological dependent mouse, and to reveal the potential neuromechanism of addictive memory by the low frequency electroacupuncture.To provide experimental evidence of preventing relapse with the acupounture.
Method:Make the experimental heroin psychological dependente model with heroin conditioned place preference(CPP) in mice,48 mice were equally and randomly divided into 3 groups after pretesting:a control group,a model group and an electroacupuncture(EA) therapy group,needling the "Neiguan(PC6)" "Shanyinjiao(SP6)" "Sisheng chong" points.The behaviour index was measured by CPP(conditioned place preference),and the expression of CaM,CaMKⅡa,p—CREB in the hippocampus measured by RT-PCR and Western Blotting.
Result:1.The mice of the model group stayed longer in the heroin-paired chamber than that of control group(P＜0.01);the therapy group stayed shorter than the model group.2.CaM and CaMKⅡa mRNA expression in hippocampus of model group increased compared with control group(P＜0.05); the expression of CaM and CAMKⅡa mRNA was decreased after EA therapy.3.Compared with control group,CaMKⅡa and p—CREB protein expression in hippocampus of model group mice rised significantly(P＜0.05), the expression of CaMKⅡa and p—CREB protein reduced in the therapy group(P＜0.05).
Conclusion:Electric needling the points could partly quench the craving by heroin-related cues,possibly through to regulate the Ca~(2-) signaling pathway and the expression of p—CREB protein in the hippocampus of mice with psychological dependence on heroin,and to interfere in the process of addiction memory consolidated by EA therapy.
引文
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