摘要
背景:从植物中尤其是传统中草药中寻找高效、低毒的抗抑郁药成为现代抗抑郁治疗的研究热点。目的:采用行为实验和神经化学方法探讨姜黄素的抗抑郁作用及其可能的作用途径。设计:随机分组设计,对照实验。单位:北京大学基础医学院药理学系。材料:实验于2003-11/2004-10在北京大学医学部药理学系实验室完成。选用雄性ICR小鼠240只。方法:共4个分实验。①拮抗利血平诱导小鼠体温下降实验:选用小鼠60只,随机分成6组:对照组,姜黄素1.25,2.50,5.00,10.00mg/kg组,盐酸丙咪嗪组(10mg/kg)。实验前先测定小鼠的正常体温,然后每组小鼠皮下注射利血平(2.5mg/kg)。18h后分别给予不同浓度的姜黄素(灌胃)、花生油(0.1mL/10g,灌胃)以及盐酸丙咪嗪(10mg/kg,腹腔注射),分别测定给药后60,90,120,150,180min小鼠的直肠温度。②5-羟色胺酸诱导的小鼠甩头实验:小鼠分组同上,阳性对照药换为盐酸氟西汀。小鼠分别灌胃给予姜黄素4个剂量同前,花生油和氟西汀(10mg/kg),1h后从小鼠尾静脉注射5-羟色胺酸(70mg/kg),观察并记录小鼠在给予5-羟色胺酸后5～10min内的甩头次数。③高剂量阿扑吗啡诱导的小鼠体温下降实验:小鼠分组同上,阳性对照药为盐酸丙咪嗪。小鼠分别灌胃给予4个剂量同前的姜黄素,花生油和盐酸丙咪嗪,1h后分别皮下注射高剂量的阿扑吗啡(16mg/kg),分别测定注射阿扑吗啡前及注射后30和60min的直肠温度。④测定小鼠脑内单胺和其代谢产物的含量:小鼠分组同上,阳性对照药为盐酸丙咪嗪。小鼠灌胃分别给予4个剂量同前的姜黄素,花生油和盐酸丙咪嗪。用高效液相电化学法测定小鼠脑内单胺及其代谢产物含量。⑤组间比较采用Dunnett’st检验。主要观察指标:①在利血平诱导的小鼠体温下降实验中,给药前后体温的变化。②在5-羟色胺酸诱导小鼠甩头实验中,给药后甩头次数是否增加。③在阿扑吗啡诱导体温下降实验中,给药后体温的改变。④测定药物对单胺递质含量的影响。结果:小鼠240只均进入结果分析。①利血平诱导的小鼠体温下降实验结果:5.00mg/kg和10.00mg/kg姜黄素可以逆转利血平诱导的小鼠体温下降,结果与对照组差异明显(P<0.05,0.01)。姜黄素在10.00mg/kg剂量下的作用与阳性对照药盐酸丙咪嗪相似。②5-羟色胺酸诱导的小鼠甩头实验结果:姜黄素(5,10mg/kg)能显著增加5-羟色胺酸诱导的小鼠的甩头次数(P<0.05,0.01)。③阿扑吗啡诱导体温下降实验结果:5.00mg/kg和10.00mg/kg姜黄素可以明显拮抗高剂量阿扑吗啡引起的小鼠体温下降,与对照组差异明显(P<0.05,0.01)。④姜黄素在2.50,5.00和10.00mg/kg剂量可以显著增加小鼠脑内5-羟色胺的含量,在10mg/kg剂量可以显著增加小鼠脑内去甲肾上腺素、多巴胺的含量。与对照组差异明显(P<0.05)。而姜黄素对其代谢产物5-羟基吲哚乙酸和3,4-二羟基苯乙酸的含量没有明显影响。阳性对照药盐酸丙咪嗪10mg/kg可以显著增加小鼠脑内5-羟色胺和去甲肾上腺素含量(P<0.05)。结论:姜黄素具有抗抑郁作用,其作用发挥可能与单胺神经系统有关。
BACKGROUND： The development of safe and powerful antidepressant agents from traditional Chinese herbs has become a hotspot in studies on anti-depression therapy. OBJECTIVE： To investigate the anti-depressive effect and possible mechanism of curcumin by behavioral and neurochemical procedures. DESIGN： Randomized grouping design and controlled experiment. SETTING： Depart, ment of Pharmacology, School of Basic Medical Sciences of Peking University.MATERIALS： This study was carried out in the laboratory of the Department of Pharmacology, School of Basic Medical Sciences of Peking University, between November 2003 and October 2004. A total of 240 male ICR mice were recruited. METHODS： The whole experiment was divided into 4 tests. ① Antagonism of reserpine-induced hypothermia： Totally 60 mice were randomly chosen and divided into 6 groups： normal control group, groups of various doses of curcumin （1.25, 2.50, 5.00 and 10.00 mg/kg）, and positive control group （imipramine 10 mg/kg）. Normal temperature of the mice was measured before experiment. The animals were given a single injection of reserpine （2.5 mg/kg）. The mice were administered with drugs 18 hours later, namely, curcumin of different concentrations by gastric perfusion, groundnut oil （0.1 mL/10g by gastric perfusion） as well as imipramine （10 mg/kg by intraperitoneal injection）. Rectal temperature was measured 60, 90, 120,150 and 180 minutes after administration, respectively. ② Potentiation of 5-hydroxytryptophan （5-HTP）-induced head twitches： animal grouping was the same as above, and the drug in positive control group was replaced by fluoxetine. The mice received gastric perfusion and the dose of curcumin given was the same as above. Groundnut oil and fluoxetine （10 mg/kg） and 5-HTP （70 mg/kg） were injected into the vein of the tail one hour later.The number of head twitches was counted within 5-10 minutes after 5-HTP treatment. ③ Antagonism of apomorphine-induced hypothermia： Mice grouping was the same as above; the drug in positive control group was replaced by imipramine. Curcumin was give as above at 4 doses, and groundnut oil and imipramine were also given. Large-dose apomorphine was injected subcutaneously （16 mg/kg）. Rectal temperature was measured before injection, as well as 30 minutes and 60 minutes after injection. ④Determination of monoamine and metabolites： Mice grouping was the same as above. The drug in positive control group was replaced by imipramine.Curcumin was give as above at 4 doses, and groundnut oil and imipramine were also given. The content of monoamine and metabolites in the mice was measured with high performance liquid chromatography. ⑤ Dunnett＇s t test was used for comparison between groups.MAIN OUTCOME MEASURES： ① In reserpine-induced hypothermia test, the change of body temperature before and after administration. ② In 5-HTP-induced head twitches test, whether the times of head twitches were increased. ③ In apomorphine-induced hypothermia test, the change of body temperature after administration. ④ Effect of drugs on the content of monoamine.RESULTS： Totally 240 mice entered the result analysis. ① Experiment results of reserpine-induced hypothermia： Curcumin （5 mg/kg and 10 mg/kg）produced an antagonism against reserpine-induced hypothermia, and the results were significantly different from those in control group （P ＜ 0.05,P＜0.01）. Curcumin of 10.00 mg/kg produced the similar effect compared as that of imipramine in positive control group. ② Results of 5-HTPinduced head twitches： Curcumin （5 and 10 mg/kg） could significantly increase the times of 5-HTP-induced head twitches （P ＜0.05, P＜0.01）. ③Results of apomorphine-induced hypothermia test： 2.50, 5.00 mg/kg and 10.00 mg/kg of curcumin could significantly increase the content of 5-HTP, and 10 mg/kg of curcumin could significantly increase the content of norepinephrine and dopamine. There was significant difference from that in control group （P ＜ 0.05）. By contrast, curcumin had no obvious effect on the content of metabolite 5-hydroxyindol acetic acid and 3,4-dihydroxyphenylacetic acid. Imipramine of 10 mg/kg as the positive control drug could significantly increase the content of 5-hydroxyindol acetic acid and norepinephrine （P＜0.05）.CONCLUSION： Curcumin has an antidepressant effect and the effect exerted may be related to monoaminergic neurotransmitter system.
出处
《中国临床康复》
CSCD
北大核心
2005年第44期162-164,共3页
Chinese Journal of Clinical Rehabilitation
