夜来香提取物对小鼠的镇痛作用

背景:夜来香水提取物具有抗心律失常、局部麻醉以及中枢抑制作用。目的:探讨夜来香提取物对小鼠的镇痛作用,为临床疼痛治疗寻找新药。设计:随机对照观察。单位:赣南医学院现代教育中心与药理教研室。材料:实验于2005-03/04在赣南医学院科研中心实验室完成。①选取健康成年昆明种小鼠150只用于以下4个独立实验。②药品:夜来香提取物由沈阳药科大学植化教研室提供(药品批号:2002080901);盐酸吗啡注射液(沈阳第一制药厂,批号000305);盐酸纳洛酮注射液眼盐侨(湖南)制药有限公司,批号20021109演。方法:①夜来香提取物对醋酸引起小鼠扭体反应的实验:小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,0.10mg/g氨基比林。15min后腹腔注射6g/L冰醋酸0.01mL/g,观察记录15min内各组小鼠扭体反应次数。②夜来香提取物对小鼠热板法致痛作用的实验:雌性小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,0.01mg/g吗啡,用热板法测定给药后15,30,60min的痛觉反应。③纳洛酮拮抗吗啡、夜来香提取物对小鼠热板法致痛作用的实验:雌性小鼠30只,随机数字表法分为3组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.004mg/g纳洛酮 0.01mg/g吗啡,0.004mg/g纳洛酮 0.10mg/g夜来香提取物,热板法测定给药后15,30,60min的痛觉反应。④夜来香提取物对电刺激致痛的实验:小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,1g/L吗啡,于给药后20,35,50,70min重复电刺激,电刺激法测定痛觉反应。主要观察指标:①小鼠扭体反应次数。②热板法致小鼠痛觉反应的时间。③电刺激法致小鼠镇痛率。结果:共选取健康成年昆明种小鼠150只用于4个独立实验,全部进入结果分析。①小鼠扭体反应次数:0.10,0.20mg/g夜来香提取物及0.10mg/g氨基比林对醋酸诱发小鼠扭体反应有非常显著的镇痛作用,给药后扭体反应次数均少于生理盐水组(20.2±10.8,14.5±7.6,7.6±4.5,50.6±15.5,P<0.01),且夜来香提取物的镇痛效果呈剂量依赖性。②热板法致小鼠痛觉反应的时间:0.10,0.20mg/g夜来香提取物对热板致痛有显著的镇痛作用,给药后15,30,60min痛觉反应的时间均长于生理盐水组(P<0.05或0.01),且呈剂量依赖性。纳洛酮0.004mg/g 夜来香提取物0.10mg/g组给药后各时间点痛觉反应的时间均长于生理盐水组(P<0.05或0.01),但纳洛酮0.004mg/g 吗啡0.01mg/g组与生理盐水组相接近。③电刺激法致小鼠镇痛率:夜来香提取物0.10,0.20mg/g组及吗啡组给药后20,35,50,70min镇痛率均高于生理盐水组(P<0.01)。结论:夜来香提取物具有明显的镇痛作用,且镇痛强度呈剂量依赖性。其镇痛作用并非通过激动阿片受体而实现的。

Analgesic effect of Cestrum nocturnum L. extract on mice

BACKGROUND: It has been considered that Cestrum nocturnum L. (CNL) has the effects of antiarrhythmia, local anesthesia and central inhibition.OBJECTIVE: To investigate the analgesic effect of CNL extract on mice,so as to find new drugs for clinical treatment of pain.DESIGN: A randomized control observation.SETTING: Center of Modern Education and Department of Pharmacology,Gannan Medical College.MATERIALS: The experiments were carried out in the laboratory of scientific research center, Gannan Medical College between March and April in 2005. ① A total of 150 healthy adult Kunming mice were used in four independent experiments. ② Drugs: CNL extract was provided by the Department of Phytochemistry, Shenyang Pharmaceutical University (batch number: 2002080901), morphine hydrochloride injection by Shenyang No.1Pharmaceutical Factory (batch number: 000305), and naloxone hydrochloride injection by Yanqiao (Hunan) Pharmaceutical Co. Ltd., (batch number:20021109).METHODS: ① Effects of CNL extract on writhing times induced by acetic acid: Forty female mice were randomly divided into four groups with 10 mice in each, and they were treated with intraperitoneal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 0.10 mg/g aminophenazone respectively. The intraperineal injection of 6 g/L glacial acetic acid was given after 15 minutes. The writhing times of mice within 15 minutes were observed and recorded in each group. ② Effects of CNL extract on the pain induced by hot pla in mice: Forty female mice were randomly divided into four groups with 10 mice in each, and they were treated with intraperineal injections of 0.02 mL/g saline, 0. 10 and 0.20 mg/g CNL extract and 0.10 mg/g morphine respectively. The pain responses were detected at 15, 30 and 60 minutes after administration. ③ The antagonistic effect of naloxone on morphine and CNL extract to the pain induced by hot plate in mice: Thirty female mice were randomly divided into three groups ith 10 mice in each group, and they were given intraperitoneal injections of 0.02 mL/g saline, naloxone 0.004 mg/g +morphine 0.01 mg/g and naloxone 0.004 mg/g+CNL extract 0.01 mg/g respectively. The pain responses were detected at 15, 30 and 60 minutes after administration respectively. ④ Effects of CNL extract on electrostimulation induced pain in mice: Forty mice were randomly divided into four groups with 10 mice in ach group, and they were administrated with intraperineal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 1 g/L morphine respectively. Repeated electrostimulations were given at 20, 35, 50 and 70minutes after administration, and the pain responses were detected by means of electrostimulation.MAIN OUTCOME MEASURES: ① Writhing times; ② Time for the pain response induced by hot plate; ③ Analgesic rate induced by electrostimulation.RESULTS: Totally 150 healthy adult Kunming mice were used in the four independent experiments, and all were involved in the analysis of results. ①Writhing times in the mice: 0.10 and 0.20 mg/g CNL extracts and 0.10 mg/g aminophenazone had very significant analgesic effects on writhing induced byacetic acid in mice, and the writhing times after administration were all fewer than those in the saline group (20.2±10.8, 14.5±7.6, 7.6±4.5,50.6±15.5, P ＜ 0.01), and the analgesic effects of CNL extract were dosedependently. ② Time for the pain response induced by hot plate: 0.10 and 0.20 mg/g CNL extracts had significant analgesic effects on the pain in duced by hot plate, and the time for pain sensation at 15, 30 and 60 minutes after administration were all longer than those in the saline group (P ＜ 0.05 or P ＜ 0.01), and the analgesic effect was dose-dependently. The times for pain sensation at each time point after administration in the naloxone 0.004 mg/g+CNL extract 0.01 mg/g group were all longer than those in the saline group, but those were close between the naloxone 0.004 mg/g+morphine 0.01 mg/g group and the saline group. ③ Analgesic rate induced by electrostimulation in the mice: The analgesic rates at20, 35, 50 and 70minutes after administration in the CNL extract 0.10 and 0.20 mg/g groups were all higher than those in the saline group (P ＜ 0.01).CONCLUSION: Our data suggested that CNL extract has obvious analgesic effect, and the analgesic intensity is dose-dependently. Naloxone, an opiate receptor antagonist, can antagonize the analgesic effect of morphine,but cannot antagonize that of CNL extract on mice with pain induced by hot plate, which indicates that CNL extract exert its analgesic role not through binding with opiate receptor.