低频电针对海洛因依赖小鼠康复期海马NMDA受体及转录因子CREB1的影响
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摘要
目的：通过观察低频电针对海洛因心理依赖小鼠康复期海马N-甲基-D-天冬氨酸(NMDA) (NR1、NR2A、NR2B)及转录因子cAMP反应元件结合蛋白1(CREBl)的影响,探讨低频电针对海洛因成瘾记忆干预作用的可能性中枢机制,深入揭示针刺防复吸的作用机理。
方法：筛选无天然位置偏爱的60只昆明种小鼠,随机分为空白组、模型组、模针组、模药组。海洛因剂量递增注射结合CPP训练制作海洛因心理依赖模型,电针“内关”、“三阴交”,点刺“四神聪”穴。采用白箱CPP值变化评价低频电针治疗效应,以免疫组化和原位杂交方法检测海马NMDA受体亚型(NR1、NR2A、NR2B)及转录因子CREB1的表达。
结果：1、模针组白箱CPP值较模型组明显降低(P<0.05)。2、模针组小鼠海马DG、CA1、CA3、CA4区NMDAR1及海马DG、CA1、CA3区NMDAR2B阳性表达较模型组增强(P<0.05)。3、模针组小鼠海马DG, CA1、CA4区NMDAR2A、CREB1阳性表达较模型组降低(P<0.05)。
结论：1、低频电针能淡化海洛因心理依赖小鼠的成瘾记忆。2、低频电针能增强海洛因心理依赖小鼠海马NMDAR1、NMDAR2B,降低NMDAR2A、CREB1的阳性表达。3、低频电针可能通过增强海马DG、CA1、CA3、CA4区NMDAR1及DG、CA1、CA3区NMDAR2B表达,降低海马DG、CA1、CA4区NMDAR2A. CREB1 mRNA表达而淡化成瘾记忆。
Objective Through researching the effect on the N-methyl-D-aspartate(NMDA) receptor subtypes(NR1 NR2A NR2B) and transcription factor CREB1 in the hippocampus of the heroin psychological dependent mice, the thesis investigated the possible neuromechanism of the heroin addictive memory of the experimental mice treated by the electro-acupuncture with low frequency, and provided experimental evidence of preventing relapse with the acupunture.
Methods Made the experimental heroin psychological dependent model with heroin conditioned place preference (CPP) in mice,60 mice were equally and randomly divided into 4 groups after pretesting:a blank control group, a model group, a model with electro-acupuncture (EA) therapy group and a model with western medicine group. needling the " Neiguan (PC6) " "Shanyinjiao(SP6)" "Sishengchong" points. The behaviour index was measured by CPP, and the expression of NMDA receptor subtype(NR1、NR2A、NR2B) and transcription factor CREB1 in hippocampus were detected by immunohistochemistry and hybridization in situ.
Results 1. The mice of the EA group stayed longer in the heroin-paired chamber than that of model group(P<0.05).2. Comparing with model group, the expressions of NR1 in DG、CA1、CA3、CA4 regions and NR2B in DG、CA1、CA3 regions of hippocampus were increased (P＜0.05). Comparing with model group, the expressions of NR2A and CREB1 in DG、CA4、CA4 regions of hippocampus were reduced (P＜0.05).
Conclusions 1. EA could partly reduce the craving caused by heroin dependence.2. EA could increase the expressions of NR1、NR2B and reduce the expressions of NR2A、CREB1.3. The therapeutical effects of EA might be developed by increasing the expressions of NR1 in DG、CA1、CA3、CA4 regions and NR2B in DG、CA1、CA3 regions of hippocampus and reducing the expressions of NR2A and CREB1 in DG、CA1、CA4 regions of hippocampus.
方法：筛选无天然位置偏爱的60只昆明种小鼠,随机分为空白组、模型组、模针组、模药组。海洛因剂量递增注射结合CPP训练制作海洛因心理依赖模型,电针“内关”、“三阴交”,点刺“四神聪”穴。采用白箱CPP值变化评价低频电针治疗效应,以免疫组化和原位杂交方法检测海马NMDA受体亚型(NR1、NR2A、NR2B)及转录因子CREB1的表达。
结果：1、模针组白箱CPP值较模型组明显降低(P<0.05)。2、模针组小鼠海马DG、CA1、CA3、CA4区NMDAR1及海马DG、CA1、CA3区NMDAR2B阳性表达较模型组增强(P<0.05)。3、模针组小鼠海马DG, CA1、CA4区NMDAR2A、CREB1阳性表达较模型组降低(P<0.05)。
结论：1、低频电针能淡化海洛因心理依赖小鼠的成瘾记忆。2、低频电针能增强海洛因心理依赖小鼠海马NMDAR1、NMDAR2B,降低NMDAR2A、CREB1的阳性表达。3、低频电针可能通过增强海马DG、CA1、CA3、CA4区NMDAR1及DG、CA1、CA3区NMDAR2B表达,降低海马DG、CA1、CA4区NMDAR2A. CREB1 mRNA表达而淡化成瘾记忆。
Objective Through researching the effect on the N-methyl-D-aspartate(NMDA) receptor subtypes(NR1 NR2A NR2B) and transcription factor CREB1 in the hippocampus of the heroin psychological dependent mice, the thesis investigated the possible neuromechanism of the heroin addictive memory of the experimental mice treated by the electro-acupuncture with low frequency, and provided experimental evidence of preventing relapse with the acupunture.
Methods Made the experimental heroin psychological dependent model with heroin conditioned place preference (CPP) in mice,60 mice were equally and randomly divided into 4 groups after pretesting:a blank control group, a model group, a model with electro-acupuncture (EA) therapy group and a model with western medicine group. needling the " Neiguan (PC6) " "Shanyinjiao(SP6)" "Sishengchong" points. The behaviour index was measured by CPP, and the expression of NMDA receptor subtype(NR1、NR2A、NR2B) and transcription factor CREB1 in hippocampus were detected by immunohistochemistry and hybridization in situ.
Results 1. The mice of the EA group stayed longer in the heroin-paired chamber than that of model group(P<0.05).2. Comparing with model group, the expressions of NR1 in DG、CA1、CA3、CA4 regions and NR2B in DG、CA1、CA3 regions of hippocampus were increased (P＜0.05). Comparing with model group, the expressions of NR2A and CREB1 in DG、CA4、CA4 regions of hippocampus were reduced (P＜0.05).
Conclusions 1. EA could partly reduce the craving caused by heroin dependence.2. EA could increase the expressions of NR1、NR2B and reduce the expressions of NR2A、CREB1.3. The therapeutical effects of EA might be developed by increasing the expressions of NR1 in DG、CA1、CA3、CA4 regions and NR2B in DG、CA1、CA3 regions of hippocampus and reducing the expressions of NR2A and CREB1 in DG、CA1、CA4 regions of hippocampus.
引文
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