粉防己碱与可乐定对小鼠和大鼠吗啡躯体依赖的影响

目的:观察粉防己碱(Tet)与可乐定对吗啡依赖小鼠和大鼠催促戒断症状的影响。方法:采用剂量递增方式皮下注射酸吗啡,建立吗啡依赖小鼠和大鼠模型,用纳洛酮催瘾。结果:Tet 15,30或60 mg/kg,可明显抑制小鼠催促戒断后的体重下降及一些戒断体征,大鼠给予 Tet 15,30或60 mg/kg 预处理,可抑制1 h 体重下降,明显改善戒断时的行为表现,戒断症状评分随剂量增加而下降。Tet 15 mg/kg 与可乐定0.075 mg/kg 联用,对吗啡依赖小鼠和大鼠催促戒断症状有明显对抗作用。但以上处理对小鼠和大鼠的跳跃反应均无影响。结论:Tet 可缓解吗啡依赖小鼠和大鼠的戒断症状,小剂量 Tet 与可乐定联用可能是一种较好的用药方案。     

舒痛安汤对吗啡依赖大鼠镇痛及生殖功能的影响

目的观察舒痛安汤对吗啡依赖大鼠镇痛及生殖功能的影响，探讨其作用机理。方法建立吗啡依赖模型大鼠，采用放免法观察舒痛安汤对吗啡依赖大鼠下丘脑和血浆β-内啡肽（β-EP）、结状神经节和孤束核P物质（SP）以及血清内分泌激素的变化。结果吗啡依赖大鼠下丘脑β-EP的含量均较正常大鼠降低，舒痛安汤高剂量组可增高下丘脑D-EP含量（P〈0．01），舒痛安汤中、高剂量组可增高血浆β-EP含量（P〈0．01，P〈0．05）；吗啡依赖大鼠结状神经节和孤束核SP含量升高，舒痛安汤高剂量组可降低结状神经节和孤束核SP的含量（P〈0．01，P〈0．05）。吗啡依赖雌性大鼠血清卵泡刺激素（FSH）、雌二醇（E2）、泌乳素（PRL）均低于正常对照组，舒痛安汤中、高剂量组均可增高血清FSH、E2、PRL含量（P〈0．01，P〈0．05）；吗啡依赖大鼠睾丸酮（T）含量显著降低（P〈0．01），舒痛安汤中、高剂量组均可增高雄性大鼠血清T含量（P〈0．01），而对大鼠血清黄体生成素、PRL含量无显著影响。结论舒痛安汤可能通过改善吗啡依赖大鼠下丘脑-垂体-肾上腺的变化，消除戒断症状，从而达到治疗目的。     

粉防己碱对小鼠吗啡诱导的高活性和强化效应的影响

目的：研究粉防己碱（Tet）对小鼠吗啡诱导的高活性和强化效应的影响。方法：单次给予吗啡用自主活动仪检测运动活性，利用位置偏爱实验评估吗啡的强化效应，用爬壁实验考察与多巴胺系统的关系，利用免疫组织化学方法显著脑内即刻早期基因c-fos的表达情况。结果：吗啡单次处理小鼠可诱导高活性，重复处理可产生位置偏爱，Tet30mg/kg或60mg/kg皮下注射可抑制吗啡诱导的高活性，60mg/kg抑制位置偏爱效应,而不影响小鼠的爬壁反应，Tet可抑制吗啡位置偏爱模型形成后伏隔核、腹侧被盖区及前额皮层c-fos阳性细胞的表达。结论：Tet能抑制吗啡诱导的高活性及强化效应，其效应可能与抑制特定脑区即刻早期 基因c-fos的表达有关。     

Inhibitory Effect of Bacopasides on Spontaneous Morphine Withdrawal Induced Depression in Mice

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A₃, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20–65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt‐ext BM contained Bacoside A₃ as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A₃. Copyright © 2013 John Wiley & Sons, Ltd.     

Phytotherapy of Opioid Dependence and Withdrawal Syndrome: A Review

Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, www.iranmedex.com and www.SID.com . All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available. Copyright © 2013 John Wiley & Sons, Ltd.     

吗啡依赖大鼠额叶皮质内神经甾体水平的变化

 目的探讨吗啡依赖和戒断对雄性大鼠额叶皮质内神经甾体水平的影响。方法腹腔注射递增剂量吗啡建立大鼠吗啡躯体依赖模型,纳洛酮诱发戒断症状;条件性位置偏爱实验建立吗啡精神依赖模型。高效液相色谱-质谱法测定大鼠额叶皮质和血浆中脱氢表雄酮(DHEA)及其硫酸酯(DHEAS)、孕烯醇酮(PREG)及其硫酸酯(PREGS)和别孕烯醇酮(AP)的含量。结果与对照组比较,大鼠吗啡躯体依赖形成时额叶皮质内DHEA水平显著升高(P<0.05),精神依赖形成时额叶皮质内DHEA,PREG水平显著升高(P<0.05);与纳洛酮对照组比较,纳洛酮催促吗啡戒断时大鼠额叶皮质内PREG,AP的含量显著升高(P<0.01),DHEAS水平显著降低(P<0.05)。结论吗啡依赖、戒断可影响大鼠额叶皮质内某些神经甾体的水平,表明内源性神经甾体可能参与吗啡依赖的形成。     

艾灸对吗啡依赖小鼠细胞免疫功能的影响

本文观察了艾灸“关元”穴对Ｍｏｒ依赖小鼠细胞免疫的影响。结果表明,Ｍｏｒ可抑制体重增加,降低细胞免疫功能,与正常组相比差异显著。艾灸“关元”穴可促进Ｍｏｒ依赖小鼠淋巴细胞转化,增强 ＮＫ细胞的活性,与对照组相比 Ｐ＜０．００１。提示艾灸具有增强 Ｍｏｒ依赖小鼠细胞免疫功能的作用,为灸疗脱毒促进康复的临床应用提供了实验依据。     

吗啡疫苗接种对小鼠血液及脑组织中吗啡含量的影响

 目的观察两种吗啡疫苗对吗啡依赖小鼠脑组织及血液中吗啡含量的影响。方法吗啡及吗啡半酯在碳二亚胺催化下分别与Blue Carrier(BC)载体蛋白交联,用其免疫小鼠,放射免疫分析方法检测免疫小鼠脑组织及血清中吗啡浓度的变化。结果琥珀酰化吗啡酯(M-6-S-BC)组血清中的吗啡浓度与吗啡依赖模型组比较有所增加,但无显著性差异(P>0.05),脑组织中的浓度,明显降低(P<0.01);吗啡酯(M-BC)组血清及脑组织中吗啡浓度与模型组比较差异显著(P<0.05)。结论两种吗啡疫苗都能诱导小鼠产生高滴度的抗吗啡抗体,可产生中和吗啡的作用,阻断吗啡进入大脑,减弱吗啡对中枢神经系统的影响,提示其对控制毒品复吸将有较好的应用前景。     

罗汉果皂苷抗疲劳及耐缺氧作用

目的:考察罗汉果皂苷的抗疲劳、耐缺氧作用.方法:将小鼠随机分为空白组,模型组,阳性对照组(红景天胶囊570 mg· kg-1),罗汉果皂苷高剂量( 300 mg· kg-1),中剂量(150 mg·kg-1)及低剂量组(75 mg·kg-1).连续灌胃给药21 d后采用力竭游泳实验和常压耐缺氧实验,考察罗汉果皂苷对小鼠的抗疲劳和耐缺氧能力的影响,并测定服用罗汉果皂苷后肝糖原和肌糖原的变化,及运动后血尿素氮、血乳酸含量和乳酸脱氢酶活力的变化.结果:罗汉果皂苷显著延长小鼠力竭游泳时间(P＜0.05),150,75 mg·kg-1组小鼠耐缺氧存活时间显著延长(P＜0.05).服用罗汉果皂苷后,小鼠肝糖原和肌糖原含量均显著增加(P ＜0.001),运动后血尿素氮和乳酸生成显著减少(P ＜0.001),乳酸脱氢酶活性显著增强(P＜0.05).结论:罗汉果皂苷能显著增强小鼠的抗疲劳和耐缺氧能力,其作用可能与增加机体糖原储备和加速乳酸代谢有关.     

参附注射液对吗啡依赖大鼠或断症状的治疗作用

目的：观察参附注射液对吗啡依赖大鼠戒断症状的治疗作用。方法：将大鼠随机分为正常对照组（A组）、停用吗啡组（B组）、续用吗啡组（C组）、丁内诺啡组（D组）和参附注射液低，高剂量组（E组、F组），按剂量递增方法腹腔注射吗啡制成吗啡依赖模型并分别给予不同药物后，腹腔注射盐酸纳洛酮催瘾，观察大鼠的戒断症状，体重及单胺类神经递质水平的变化。结果：经参附注射液治疗的大鼠戒断症状明显减轻，体重明显恢复，脑组织中NA、DA、5－HT等单胺类神经递质水平显著降低，结论：参附注射液对吗啡依赖大鼠具有一定治疗作用，其机理与调节单胺类神经递质的紊乱有关。     

电针对吗啡戒断后焦虑小鼠脑干c-fos表达的影响

目的：探讨电针对吗啡戒断后焦虑小鼠脑干c—fos表达的影响。方法：以昆明种小鼠为实验对象,采用逐日递增原则皮下注射吗啡形成依赖后,纳洛酮催促,建立吗啡戒断后焦虑模型;选用“三阴交”穴进行电针治疗;每天1次,每次15min,连续治疗3天。免疫组化法检测c—fos的表达。结果：与模型组相比,模针组脑干c—fos光密度值、阳性细胞数、阳性面积百分比下降,灰度值增高,差异均有统计学意义（P〈0．01）,与迷空组相比,则无明显差异。结论：电针抗吗啡戒断后焦虑效应可能与其降低脑干c—fos的表达有关。     

蝎毒与吗啡中枢镇痛作用效果比较

蝎毒及其提取物有明显的镇痛作用，我们对其中枢镇痛作用效果与吗啡进行了比较。向大鼠中脑导水管周围灰质（PAG）内微量注射蝎毒（scorpionvenom，SV）和吗啡（morphine），以热辐射甩尾法为指标，观察比较二者中枢镇痛作用效果。结果表明：向大鼠PAG内恒速注射0．025％～0．10％SV0．5μL（相当于0．5μg／kg～2μg／kg）即出现痛阈升高，20min达峰值（痛阈最大提高150％以上），与对照组比较有显著差异（P＜0．01），而欲使大鼠痛阈提高150％，PAG内注射吗啡的用量约为10μg／kg。提示SV有很强的中枢镇痛作用，作用强于吗啡4倍以上。     

电针对吗啡戒断大鼠cAMP、cGMP水平的影响

目的研究电针吗啡戒断大鼠足三里穴对大鼠环磷鸟苷酸(cyclic guanosine3',5'-monophosphate,cGMP)及环磷腺苷酸(cyclic adenosine3',5'-monophosphate,cAMP)含量的影响,探讨电针改善戒断症状作用的可能机制。方法建立吗啡依赖大鼠自然戒断模型,采用放射免疫分析法测定血液、脑组织中cGMP、cAMP含量。结果戒断Ⅰ组大鼠血液cAMP含量增高(P<0.01),cGMP含量明显降低(P<0.01),cAMP/cGMP比值显著增高(P<0.01);戒断Ⅱ组大鼠脑中cGMP、cAMP含量均明显减少(P<0.01);电针组cGMP、cAMP含量接近正常水平。结论电针足三里穴改善大鼠吗啡戒断症状可能与调节cGMP、cAMP系统的相互作用有关。     

加味参附汤对吗啡依赖戒断小鼠免疫功能的影响

吗啡依赖小鼠自然戒断后可见脾脏、胸腺萎缩，巨噬细胞Fc受体阳性百分率及吞噬功能、外周血T淋巴细胞总数、T淋巴细胞对PHA的殖反应、脾T淋巴细胞CD4^ 百分率及CD4^ /CD8^ 比值均明显下降；吗啡继续成瘾而未戒断的小鼠的以上指标进一步损伤；加味参附汤（MSFD）治疗小鼠以上指标均有不同程度的恢复；而丁丙诺啡治疗后免疫功能状态仍低于或相当于自然戒断时。提示MSFD能促进吗啡依赖戒断小鼠损伤的免疫功能的恢复，这一作用可能与其对神经内分泌系统的调节有关。     

参附注射液对吗啡依赖大鼠戒断症状及单胺类神经递质的影响

目的：观察参附注射液对吗啡依赖大鼠的戒毒作用。方法：雄性大鼠按剂量递增方法ip吗啡形成吗啡依赖模型,ip盐酸纳洛酮（1.0mg/kg）催瘾,观察戒断症状、体重及单胺类神经递质变化。结果：参附注射液能减轻大鼠的症状,恢复体重,显降低吗啡依赖大鼠催促戒断时脑组织中NA、DA、5－HT等单胺类神经递质。结论：参附注射液对吗啡依赖大鼠具有一定治疗作用,其机理与调节单胺类神经递质紊乱有关。     

The inhibitory effect of Hypericum perforatum extract on morphine withdrawal syndrome in rat and comparison with clonidine

The effects of Hypericum perforatum (St John's wort) on morphine withdrawal syndrome and comparison with clonidine have been investigated in morphine‐dependent rats. Adult male Wistar rats were subjects. The frequencies of withdrawal behavioral signs (rearing, teeth chattering and jumping) induced by naloxone challenge were demonstrated in morphine dependent rats receiving Hypericum perforatum extract (HPE), saline or clonidine. The withdrawal behavioral manifestations in rats were inhibited significantly by chronic co‐administration of Hypericum perforatum extract or clonidine with morphine. This study showed that clonidine was more effective than HPE at a dose of 0.4 mL/200 g and there was no significant statistical difference between the mean frequency of withdrawal signs of HPE at a dose of 0.8 mL/200 g compared with clonidine (0.2 mg/kg i.p.) but at a dose of 1.2 mL/200 g of HPE was significantly stronger than clonidine in attenuation of the morphine withdrawal syndrome. The findings suggest that HPE is capable of reducing the symptoms of opiate withdrawal and its effectiveness may be equivalent to clonidine in reducing the opiate withdrawal syndrome and may have human therapeutic potential. Copyright © 2009 John Wiley & Sons, Ltd.     

Oleuropein,Chief Constituent of Olive Leaf Extract,Prevents the Development of Morphine Antinociceptive Tolerance through Inhibition of Morphine‐induced L‐type Calcium Channel Overexpression

It has been shown that blockade of L‐type calcium channels could abolish the development of opioid‐induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20 mg/kg, i.p.) for 8 days to induce antinociceptive tolerance. Then OLE (50–200 mg/kg i.g.) and oleuropein (1–10 mg/kg i.p.) were injected concomitantly with morphine. The tail‐flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L‐type calcium channel using semiquantitative RT‐PCR. The results showed that OLE (200 mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10 mg/kg, but not in 5 mg/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE. In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect. Copyright © 2012 John Wiley & Sons, Ltd.     

电针对吗啡戒断大鼠一氧化氮影响的机理研究

目的探讨针刺改善吗啡戒断症状的作用机理。方法建立自然吗啡戒断大鼠模型,观察电针、L-Arg、L-NAME对吗啡戒断大鼠体重、戒断症状、脑组织和血液中NO、NOS的影响。结果与正常大鼠相比,吗啡戒断大鼠体重减轻,戒断症状明显,NO含量和NOS活性升高。电针组吗啡戒断大鼠体重增加,NO含量和NOS活性降低,与戒断组比较差异显著(P<0.05)。结论电针改善戒断症状的作用与NOS阻断剂L-NAME相似,调节NOS活性可能是电针改善吗啡戒断症状的作用机理之一。     

芫荽子挥发油中芳樟醇含量测定

目的　测定芫荽子挥发油中芳樟醇含量。方法　采用内标法 ,以乙酸龙脑酯为内标物 ,测定了陕西、北京、安徽、河南、广东等地产芫荽子挥发油中芳樟醇含量。结果　不同产地的芫荽子挥发油含量以及挥发油中芳樟醇含量均有一定差异。结论　方法简单 ,重现性好 ,可作为芫荽子挥发油中芳樟醇含量测定方法     

丹参提取物对小鼠吗啡身体依赖性的影响

目的观察丹参提取物对小鼠吗啡身体依赖性的影响。方法反复sc吗啡建立小鼠吗啡身体依赖模型,以ip纳洛酮诱发其戒断症状。分别在建立吗啡依赖模型同时或建立后ip给予不同剂量的丹参提取物,观察长期预防性给药和急性给药对小鼠纳洛酮催促后戒断反应症状的影响,并且观察丹参提取物自身潜在的身体依赖性。结果和吗啡模型组相比,丹参提取物长期预防性给药(100~200 m g/kg),小鼠跳跃数减少(P<0.05),预防性给药(200 m g/kg)组体重下降也显著改善(P<0.05);急性给药(500 m g/kg)能明显减少吗啡依赖小鼠的跳跃数(P<0.05),急性给药(200~500 m g/kg)能一定程度改善体重的下降,但无统计学意义;丹参提取物长期给药不存在自身的身体依赖性。结论丹参提取物在一定程度上抑制小鼠吗啡身体依赖的形成,可以缓解吗啡依赖小鼠的戒断症状,且自身无潜在身体依赖性。