内源性大麻素受体在电针防治大鼠海洛因复吸中的作用及机制研究

Prevention of heroin relapse is an urgent medical and social problem. Electroacupuncture is one of the effective auxiliary means for treating drug abuse, but the mechanism is still needed to be further researched. Existing studies showed that endogenous cannabinoid receptors were closely related to heroin relapse. Our previous work found that in addiction rats electroacupuncture has "two-way adjustment" effect on the endogenous cannabinoid receptors. We also found that some miRNA levels are associated with endogenous cannabinoid receptor expression levels in addicted rats. Therefore, we plan to use the rat intravenous heroin self-administration model and apply different frequencies of electroacupuncture stimulus to acupoints. We want to investigate the influences of electroacupuncture on heroin relapse, the expression changes of endogenous cannabinoid receptors and the dopamine levels of the meolimbic dapamine system for deeply understanding the potential interaction among them via reverse transcription-polymerase chain reaction, immunohistochemistry and high performance liquid chromatography technologies. By use of the miRNA screening and verification technology, we will inspect that micrornas regulation and regularities of the expression of endogenous cannabinoid receptors. The aim of this study is to ultimately prove that acusector can "two-way adjustment" endogenous cannabinoid receptors, then induce dopamine levels back to normal to prevention and treatment of heroin relapse. Among them, the electroacupuncture regulation mechanism for the endogenous cannabinoid receptors can be realized through adjusting the miRNA expression.

防治海洛因复吸是亟待解决的医学难题。已有证据提示内源性大麻素1型和2型受体（CB1-R和CB2-R）都参与调节脑内"奖赏系统"多巴胺含量，与海洛因复吸行为密切相关。电针是防复吸有效的辅助性治疗手段之一，本项目组在围绕电针防治海洛因复吸的相关研究中发现，2Hz电针可以显著减少海洛因成瘾大鼠的静脉自身给药行为，同时使其复吸相关核团中大麻素1型及2型受体表达发生显著变化；另外还发现成瘾大鼠脑内某些miRNA水平与内源性大麻素受体表达水平关系密切。本项目采用已稳定建立的大鼠海洛因静脉自身给药模型，运用聚合酶链式反应、免疫组化及高效液相色谱分析等技术，深入考察电针对大鼠海洛因复吸行为、内源性大麻素受体表达以及多巴胺含量的影响，以探明电针是否通过调节CB1-R和CB2-R这一途径最终达到防治海洛因复吸的目的；在此基础上，运用miRNA筛选及验证技术，探讨电针在基因转录水平对内源性大麻素受体调控的机制。

防治海洛因复吸是亟待解决的医学难题。内源性大麻素1型和2型受体（CB1-R和CB2-R）都参与调节脑内"奖赏系统"多巴胺含量，与海洛因复吸行为密切相关。电针是防复吸有效的辅助性治疗手段之一。本项目采用已稳定建立的大鼠海洛因静脉自身给药模型，运用聚合酶链式反应、免疫组化及高效液相色谱分析等技术，深入考察电针对大鼠海洛因复吸行为、内源性大麻素受体表达的影响，本项目组在围绕电针防治海洛因复吸的相关研究中发现，2Hz电针可以显著减少海洛因成瘾大鼠的静脉自身给药行为，同时使其复吸相关核团中大麻素1型及2型受体表达发生显著变化，证明2Hz电针可以通过调节CB1-R和CB2-R这一途径达到防治海洛因复吸的目的。项目中考察电针对大鼠海洛因复吸行为和脑内DA含量变化的影响仍在积极探讨中。筛选出来的mirRNA378b及其主要靶基因CB1R在电针干预大鼠海洛因复吸作用正在进行验证。疼痛是海洛因成瘾戒断后复吸以及临床阿片类药物镇痛发生耐受乃至诱发痛敏的原因之一,研究中还发现成瘾大鼠痛敏行为显著增加，同时初级感觉神经元DRG上P2X3受体表达显著上调。2Hz电针可以显著减少海洛因成瘾大鼠的痛敏行为，同时显著减少初级感觉神经元DRG上P2X3受体表达，证明2Hz电针还可以通过调节外周初级感觉神经元DRG上P2X3受体这一途径抑制外周痛敏，从而发挥防治海洛因复吸的作用。鉴于新型毒品（人工合成兴奋性毒品）成瘾的泛滥已经大有超越传统毒品成瘾泛滥的趋势，我们的研究焦点也进一步关注新型毒品成瘾及其脑损伤保护的机制研究及其防治。我们已经在进行相关预实验以期初步验证猜想，为下一步申请国家自科基金资助打下良好基础。