URWell对吗啡依赖小鼠戒断反应和NO/NOS系统的影响

Effects of URWell on Withdrawal Syndrome and NO/NOS System in Morphine-dependent Mice

目的:研究中药URWell对吗啡依赖小鼠催促戒断症状及其一氧化氮(NO)/一氧化氮合酶(NOS)系统的影响,初探其作用机制。方法:取昆明种小鼠60只,随机分为正常对照组,模型组,阳性对照组(可乐定,0.4 mg.kg-1.d-1,ig),URWell组(以生药计剂量分别为20,10,5 g.kg-1.d-1,ig)。除正常对照组外,各组以剂量递增法连续皮下注射吗啡,建立吗啡依赖模型,于建模第5天开始各组分别给予相应的药物,连续给药6 d。各组于建模第8天,予以纳络酮(4 mg.kg-1,ip)催促戒断,观察小鼠2 h内的戒断症状和体重变化。用硝酸还原酶法测定各组小鼠大脑组织匀浆的NO含量与NOS活性。结果:与模型组比较,URWell组(20,10 g.kg-1.d-1)小鼠在第8,9天跳跃反应明显降低(P<0.05),可乐定组和URWell组(20,10 g.kg-1.d-1)小鼠戒断后体重降低明显减少(P<0.05),可乐定组和URWell组(20g.kg-1.d-1)小鼠大脑NO含量及NOS活性下降(P<0.05)。结论:URWell能抑制吗啡依赖小鼠催促戒断症状,其作用机制可能与URWell影响大脑的NO/NOS系统有关。

Objective： To observe the effects of URWell on withdrawal syndrome and nitricoxide（NO）/nitric oxide synthase （NOS） system in morphine-dependent mice and its action mechanisms. Method： Sixty mice were divided into 6 groups randomly, namely the control group, model group, positive control group（clonidine, 0.4 mg·kg-1·d-1, ig）, URWell group （20, 10, 5 g·kg-1·d-1, ig）.Except the control group, the morphine-dependent mice model of other groups was established by administration of gradually increasing doses of morphine.Oral URWell or saline （control, model） was administered from the 5th day to the 10th day.The acute withdrawal was induced by naloxone （4 mg·kg-1, ip） in the 8th day, then withdrawal syndrome and body weight loss were recorded.NO concentration and NOS activity in brain tissues were tested by nitrate reductase method. Result： Compared with the model group, URWell （20, 10 g·kg-1）, respectively, significantly suppressed morphine withdrawal syndrome within the 8th day and 9th day（P〈0.05）, clonidine and URWell （20, 10 g·kg-1·d-1） significantly reduced body weight loss in morphine-dependent mice following morphine withdrawal, as well as clonidine and URWell（20 g·kg-1）significantly inhibited levels of NO and NOS in brain tissues. Conclusion： URWell treatment attenuated withdrawal syndrome in morphine-dependent mice, and the mechanism may be associated with inhibiting NO and NOS in the brain.