和厚朴酚与厚朴酚在缓解大鼠吗啡戒断反应中对β-内啡肽的影响

背景现代药理证实和厚朴酚与厚朴酚具有中枢抑制作用和肌肉松弛作用,且有报道证实其可缓解动物吗啡依赖戒断症状.目的探讨和厚朴酚与厚朴酚在缓解吗啡戒断反应中对β-内啡肽的影响.设计随机对照实验.单位湖北民族学院医学院药理学教研室.对象实验于2003-04-13/29进行,取成年雄性SD大鼠100只,其中30只大鼠作为对照组随机分成生理盐水组、和厚朴酚组和厚朴酚组各10只,另外70只大鼠作为吗啡依赖组,随机分成生理盐水组,和厚朴酚5,40,80mg/kg组与厚朴酚5,40,80 mg/kg组7组,各10只.方法对照组中3个亚组分别腹腔注射生理盐水0.2 mL、和厚朴酚与厚朴酚各80 mg/kg.吗啡依赖组大鼠逐日增量皮下注射吗啡6 d,建立急性吗啡依赖大鼠及吗啡自然戒断模型,在第6天900最后一次给吗啡后,1030腹腔注射给药,生理盐水组给予生理盐水0.2 mL,其他6组分别给予和厚朴酚、厚朴酚各5,40和80 mg/kg.于1100分别观察吗啡依赖组每只大鼠1 h内各项自然戒断症状.主要观察指标①各组大鼠脑脊液中β-内啡肽水平.②比较吗啡依赖组中7个亚组大鼠自然戒断症状评分.结果①脑脊液中β-内啡肽水平对照组中和厚朴酚与厚朴酚组显著高于生理盐水组(P＜0.01),而且和厚朴酚强于厚朴酚(P＜0.05).吗啡依赖+生理盐水组明显低于对照+生理盐水组(P＜0.01).吗啡依赖组中和厚朴酚与厚朴酚5,40,80 mg/kg组均高于生理盐水组(P＜0.01),而且呈量效关系.②吗啡依赖组大鼠自然戒断症状评分和厚朴酚与厚朴酚各剂量组湿狗样抖动、舔阴,逃避症状得分均低于生理盐水组(P＜0.05,0.01),且剂量越大效果越显著;和厚朴酚与厚朴酚40,80 mg/kg组咬牙、扭体及体质量丢失显著低于生理盐水组(P＜0.01).结论和厚朴酚与厚朴酚可明显抑制吗啡戒断反应,且抑制效应呈量效关系,这一抑制效应与脑内β-内啡肽的增加有关.这种效应对吗啡依赖大鼠和厚朴酚与厚朴酚相当,对正常大鼠和厚朴酚强于厚朴酚.

Effects of honokiol and magnolol on beta-endorphin in relieving morphine withdrawal symptoms in rats

BACKGROUND: It has been verified pharmacologically that honokiol (HL) and magnolol (ML) have distinct effects on central inhibition and muscle relaxation, and some reports prove that they can relieve morphine withdrawal symptoms in animals.OBJECTIVE: To explore the effects of HL and ML on β-endorphin (β-EP) in relieving morphine withdrawal symptoms in rats.DESIGN: Randomized controlled study.SETTING: Pharmacological Department, the Medical School of Hubei national College.PARTICIPANTS: The experiment was conducted from 13 to 29 April,2003. Among 100 adult male SD rats, 30 rats as control group were randomly divided into three subgroups: saline group, HL group and ML group with 10 in each group. The other 70 rats as morphine-dependent group were divided into normal saline group, 5, 40 and 80 mg/kg HL and ML groups with 10 in each group.METHODS: 0.2 mL normal saline, 80 mg/kg HL and 80 mg/kg ML were injected intraperitoneally into rats in control group. The dose of morphine subcutaneously injected was increased in the rats in morphine-dependent group for 6 days to establish the model of acute morphine dependence and model of natural morphine withdrawal symptoms. The last injection was performed at 9:00 on the morning of day 6, and the intraperitoneal injection was performed at 10:30 on the same morning. 0.2 mL normal saline was injected into the rats of saline group. 5, 40 and 80 mg/kg HL and 5,40 and 80 mg/kg ML were given to rats in the other six groups, respectively. Starting from 11:00, half an hour later, all natural morphine withdrawal symptoms were observed in rats within an hour.compared among rats in the 7 morphine-dependent subgroups.control groups than in normal saline group (P ＜ 0.01), and HL group had higher β-EP level than ML group (P ＜ 0.05). β-EP level was obviously lower in morphine-dependent+saline groups than in control+saline groups (P ＜ 0.01).β-EP level in morphine-dependent+5, 40 and 80 mg/kg HL groups and in morphine-dependent+5, 40 and 80 mg/kg ML groups was obviously higher Scores of natural morphine withdrawal symptoms in rats of morphine-dependent group: Scores of wetshakes, penile licking, escape attempts, and weight lost in HL and ML subgroups were obviously lower than those in saline group (P ＜ 0.01).CONCLUSION: HL and ML can markedly restrain morphine withdrawal symptoms and this restraint is related to the increase of β-EP level in the brain. HL and ML have equal inhibitory effects on morphine-dependent rats, but HL is more effective than ML in normal rats.