藁本内酯对吗啡依赖大鼠戒断症状及脑内单胺类神经递质的影响

Effects of Ligustilide on the withdrawal syndromes and monoamine neurotransmitters in brain of morphine-dependent rats

目的探讨藁本内酯对大鼠吗啡戒断症状及下丘脑和伏隔核中单胺类神经递质释放的影响。方法将60只SD大鼠按照随机数字表法均分为空白对照组、模型组、可乐定组和藁本内酯高(80mg/kg)、中(40mg/kg)和低(20mg/kg)剂量组,每组10只。采用剂量递增法颈背部皮下注射吗啡建立大鼠吗啡依赖模型,腹腔注射纳络酮催促戒断反应,采用柳田知司法对大鼠戒断症状进行评分。采用酶联免疫吸附法(ELISA)检测下丘脑和伏隔核中去甲肾上腺素(NE)、多巴胺(DA)和五羟色胺(5-HT)含量。结果空白对照组、模型组、可乐定组、藁本内酯低、中和高剂量组躯体戒断症状总评分值依次为0分、(31.83±7.33)分、(17.92±6.88)分、(25.58±5.99)分、(19.88±4.82)分和(16.75±4.01)分,相对于模型组,藁本内酯低、中和高剂量组和可乐定组依赖地减弱大鼠纳络酮催促吗啡戒断症状,降低戒断症状总评分值降低(均P<0.05)。与空白对照组比较,模型组下丘脑和伏隔核中NE、DA及5-HT的含量均升高(均P<0.01);相对于模型组,藁本内酯低、中和高剂量组和可乐定组下丘脑和伏隔核中NE、DA及5-HT的含量均降低(均P<0.05)。结论藁本内酯有效减弱大鼠纳络酮催促吗啡戒断症状,其机制可能与抑制下丘脑和伏隔核中单胺类神经递质的过度释放有关。

Objective To investigate the effects of Ligustilide on the withdrawal syndromes syndromes and monoamine neurotransmitters of hypothalamus and nucleus accumbens in morphine-dependent rats.Methods Totally 60 SD rats were divided into control group,model group,clonidine group and Ligustilide high(80 mg/kg),medium(40 mg/kg)and low(20 mg/kg)dose group according to the random number table with 10 in each group.Rats were given in gradual increasing doses of morphine to produce physical dependence.Morphine withdrawal syndrome was precipitated by naloxone and withdrawal symptoms were evaluated by Ryuta Tomoji score.The level of norepinephrine(NE),dopamine(DA)and 5-hydroxytryptamine(5-HT)in rats were tested with enzyme-linked immunosorbent assay(ELISA).Results The total score of somatic withdrawal syndromes in the control group,model group,clonidine group and Ligustilide low,medium and high dose group were 0,(31.83±7.33),(17.92±6.88),(25.58±5.99),(19.88±4.82)and(16.75±4.01).Compared with the model group,the morphine withdrawal syndromes scores of Ligustilide low,medium and high dose groups and clonidine group were reduced(all P<0.05).The level of NE,DA and 5-HT in hypothalamus and nucleus accumbens were increased compared with that of control group.Compared with the model group,the level of NE,DA and 5-HT in hypothalamus and nucleus accumbens of Ligustilide low,medium and high dose groups and clonidine group were significantly reduced(P<0.05).Conclusion Ligustilide can effectively alleviate the symptoms in morphine-withdrawal rats,which may be related to the inhibition of excessive release of monoamine neurotransmitters in hypothalamus and nucleus accumbens.