针刺太冲穴对海洛因成瘾模型大鼠脑功能和神经内分泌因子的影响
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摘要
目的观察针刺太冲穴对海洛因成瘾模型大鼠焦虑症状的作用,并探讨对大鼠脑功能、神经内分泌因子的影响。方法 90只大鼠分为正常对照组(A组),海洛因复吸模型组(B组)、针刺治疗组(C组)。建立海洛因成瘾动物模型,观察戒断大鼠焦虑程度及针刺的抗焦虑作用。检测大鼠全脑中单胺神经递质、血清中神经内分泌因子水平,探讨可能的作用机制。结果 B、C组扭体、湿狗样颤抖、跳跃、站立、齿颤、上睑下垂等戒断症状评分均高于A组(P<0.05);B、C组之间上述戒断症状评分比较,差异均无统计学意义(P>0.05)。B、C组进入开臂次数百分率、开臂滞留时间百分率低于A组(P<0.05),C组进入开臂次数百分率、开臂滞留时间百分率高于B组(P<0.05)。B、C组脑干去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)水平高于A组(P<0.05),B组NE、DA、5-HT水平高于C组(P<0.05)。B、C组血清N端脑钠肽前体(NT-proBNP)、血浆血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平高于A组(P<0.05),B组NT-proBNP、AngⅡ、ALD水平高于C组(P<0.05)。结论针刺太冲穴可明显改善海洛因成瘾戒断大鼠焦虑症状,可能通过减少全脑中单胺神经递质水平,降低血清中神经内分泌因子水平来实现。
Objective To observe the effect of acupuncture at Taichong point on anxiety symptoms in rat models of heroin addiction,and explore its effects on brain function and neuroendocrine factors.Methods A total of 90 rats were divided into the normal control group(group A),the heroin re-addiction model group(group B)and the acupuncture treatment group(group C).The animal models of heroin addiction were established,and the anxiety degree of withdrawal rats and the anxiolytic effect of acupuncture were observed.The levels of monoamine neurotransmitters in the whole brain of rats and serum neuroendocrine factors were detected,and the possible mechanism was explored.Results The withdrawal symptoms scores of body torsion,wet-dog shakes,jumping,standing,teeth chattering and ptosis in group B and group C were significantly higher than those in group A(P<0.05),and there was no significant difference in the above withdrawal symptoms scores between group B and group C(P>0.05).The percentage of open-arms entries and open-arms retention time in group B and group C were significantly lower than those in group A(P<0.05),and the percentage of open-arms entries and open-arms retention time in group C were significantly higher than those in group B(P<0.05).The brainstem levels of norepinephrine(NE),dopamine(DA)and serotonin(5-HT)in group B and group C were significantly higher than those in group A(P<0.05),and the levels in group B were significantly higher than those in group C(P<0.05).The levels of serum N-terminal probrain natriuretic peptide(NT-proBNP),plasma angiotensin Ⅱ(AngⅡ)and aldosterone(ALD)in group B and group C were significantly higher than those in group A(P<0.05),and the levels in group B were significantly higher than those in group C(P<0.05).Conclusion Acupuncture at Taichong point significantly alleviate anxiety symptoms in withdrawal rats of heroin addiction,which may be achieved by reducing the levels of monoamine neurotransmitters in whole brain and the levels of neuroendocrine factors in serum.
Objective To observe the effect of acupuncture at Taichong point on anxiety symptoms in rat models of heroin addiction,and explore its effects on brain function and neuroendocrine factors.Methods A total of 90 rats were divided into the normal control group(group A),the heroin re-addiction model group(group B)and the acupuncture treatment group(group C).The animal models of heroin addiction were established,and the anxiety degree of withdrawal rats and the anxiolytic effect of acupuncture were observed.The levels of monoamine neurotransmitters in the whole brain of rats and serum neuroendocrine factors were detected,and the possible mechanism was explored.Results The withdrawal symptoms scores of body torsion,wet-dog shakes,jumping,standing,teeth chattering and ptosis in group B and group C were significantly higher than those in group A(P<0.05),and there was no significant difference in the above withdrawal symptoms scores between group B and group C(P>0.05).The percentage of open-arms entries and open-arms retention time in group B and group C were significantly lower than those in group A(P<0.05),and the percentage of open-arms entries and open-arms retention time in group C were significantly higher than those in group B(P<0.05).The brainstem levels of norepinephrine(NE),dopamine(DA)and serotonin(5-HT)in group B and group C were significantly higher than those in group A(P<0.05),and the levels in group B were significantly higher than those in group C(P<0.05).The levels of serum N-terminal probrain natriuretic peptide(NT-proBNP),plasma angiotensin Ⅱ(AngⅡ)and aldosterone(ALD)in group B and group C were significantly higher than those in group A(P<0.05),and the levels in group B were significantly higher than those in group C(P<0.05).Conclusion Acupuncture at Taichong point significantly alleviate anxiety symptoms in withdrawal rats of heroin addiction,which may be achieved by reducing the levels of monoamine neurotransmitters in whole brain and the levels of neuroendocrine factors in serum.
引文
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[12]MORABBI M J,RAZAGHI E,MOAZEN-ZADEH E,et al.Pexacerfont as a CRF1antagonist for the treatment of withdrawal symptoms in men with heroin/methamphetamine dependence:a randomized,double-blind,placebocontrolled clinical trial[J].Int Clin Psychopharmacol,2018,33(2):111-119.
[13]CAROBREZ A P,BERTOGLIO L J.Ethological and temporal analyses of anxiety-like behavior:the elevated plus-maze model 20 years on[J].Neurosci Biobehav Rev,2005,29(8):1193-1205.
[14]BLUM K,LIU Y,WANG W,et al.rsfMRI effects of KB220ZTMon neural pathways in reward circuitry of abstinent genotyped heroin addicts[J].Postgrad Med,2015,127(2):232-241.
[15]KMMERER N,LEMENAGER T,GROSSHANS M,et al.Pregabalin for the reduction of opiate withdrawal symptoms[J].Psychiatr Prax,2012,39(7):351-352.
[16]MILLER D K,BOWIRRAT A,MANKA M,et al.Acute intravenous synaptamine complex variant KB220TM"normalizes"neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms:part 1,pilot study with 2case reports[J].Postgrad Med,2010,122(6):188-213.
[17]PENG X Q,XI Z X,LI X,et al.Is slow-onset long-acting monoamine transport blockade to cocaine as methadone is to heroin?Implication for anti-addiction medications[J].Neuropsychopharmacology,2010,35(13):2564-2578.
[18]JIA Y,ZHANG X,YU J,et al.Acupuncture for patients with mild to moderate Alzheimer′s disease:a randomized controlled trial[J].BMC Complement Altern Med,2017,17(1):556.
[19]YANG J,LI J,XU G,et al.Elevated hair cortisol levels among heroin addicts on current methadone maintenance compared to controls[J].PLoS One,2016,11(3):e0150729.
[20]PICETTI R,SCHLUSSMAN S D,ZHOU Y,et al.Addictions and stress:clues for cocaine pharmacotherapies[J].Curr Pharm Des,2013,19(40):7065-7080.
[21]GERBER H,BORGWARDT S J,SCHMID O,et al.The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence[J].Eur Addict Res,2012,18(3):116-123.
[2]彭艳秋,王超,赵建伟,等.成都市成华区新型毒品滥用影响因素的定性分析[J].现代预防医学,2017,44(2):336-339.
[3]GHANBARI R,SUMNER S.Using metabolomics to investigate biomarkers of drug addiction[J].Trends Mol Med,2018,24(2):197-205.
[4]KALINICHENKO L S,GULBINS E,KORNHUBER J,et al.The role of sphingolipids in psychoactive drug use and addiction[J].J Neural Transm,2018,125(4):651-672.
[5]余会平.吗啡依赖及戒断大鼠相关脑区BDNF、Bcl-2的表达及超微结构改变[D].重庆:重庆医科大学,2004.
[6]CICEK E,DEMIREL B,CICEK I E,et al.Increased neutrophil-lymphocyte and platelet-lymphocyte ratios in male heroin addicts:aprospective controlled study[J].Clin Psychopharmacol Neurosci,2018,16(2):190-196.
[7]孙红梅,吴海霞,许红,等.针刺督脉穴对帕金森病小鼠多巴胺能神经元保护及超微结构的影响[J].北京中医药大学学报,2010,33(4):257-261,289.
[8]姜伟,杨敏,余茜.针刺对脑梗死大鼠脑组织形态、能量代谢及神经保护因子表达的干预效应[J].中国临床康复,2006,10(47):115-117.
[9]华兴邦,周浩良.大鼠穴位图谱的研制[J].实验动物与动物实验,1991,3(1):1-5.
[10]PAXINOS G,WATSON C.大鼠脑立体定位图谱[M].诸葛启钏,译.北京:人民卫生出版社,2005:95-104.
[11]MALDONADO R,NEGUS S,KOOB G F.Precipitation of morphine withdrawal syndrome in rats by administration of mu-,delta-and kappa-selective opioid antagonists[J].Neuropharmacology,1992,31(12):1231-1241.
[12]MORABBI M J,RAZAGHI E,MOAZEN-ZADEH E,et al.Pexacerfont as a CRF1antagonist for the treatment of withdrawal symptoms in men with heroin/methamphetamine dependence:a randomized,double-blind,placebocontrolled clinical trial[J].Int Clin Psychopharmacol,2018,33(2):111-119.
[13]CAROBREZ A P,BERTOGLIO L J.Ethological and temporal analyses of anxiety-like behavior:the elevated plus-maze model 20 years on[J].Neurosci Biobehav Rev,2005,29(8):1193-1205.
[14]BLUM K,LIU Y,WANG W,et al.rsfMRI effects of KB220ZTMon neural pathways in reward circuitry of abstinent genotyped heroin addicts[J].Postgrad Med,2015,127(2):232-241.
[15]KMMERER N,LEMENAGER T,GROSSHANS M,et al.Pregabalin for the reduction of opiate withdrawal symptoms[J].Psychiatr Prax,2012,39(7):351-352.
[16]MILLER D K,BOWIRRAT A,MANKA M,et al.Acute intravenous synaptamine complex variant KB220TM"normalizes"neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms:part 1,pilot study with 2case reports[J].Postgrad Med,2010,122(6):188-213.
[17]PENG X Q,XI Z X,LI X,et al.Is slow-onset long-acting monoamine transport blockade to cocaine as methadone is to heroin?Implication for anti-addiction medications[J].Neuropsychopharmacology,2010,35(13):2564-2578.
[18]JIA Y,ZHANG X,YU J,et al.Acupuncture for patients with mild to moderate Alzheimer′s disease:a randomized controlled trial[J].BMC Complement Altern Med,2017,17(1):556.
[19]YANG J,LI J,XU G,et al.Elevated hair cortisol levels among heroin addicts on current methadone maintenance compared to controls[J].PLoS One,2016,11(3):e0150729.
[20]PICETTI R,SCHLUSSMAN S D,ZHOU Y,et al.Addictions and stress:clues for cocaine pharmacotherapies[J].Curr Pharm Des,2013,19(40):7065-7080.
[21]GERBER H,BORGWARDT S J,SCHMID O,et al.The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence[J].Eur Addict Res,2012,18(3):116-123.