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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 study the effect of URWell, a traditional Chinese medicine, on the withdrawal symptoms and nitric oxide (NO) / nitric oxide synthase (NOS) system in morphine-dependent mice, and to explore its mechanism of action. Methods: 60 Kunming mice were randomly divided into normal control group, model group, positive control group (clonidine, 0.4 mg.kg-1.d-1, ig), and URWell group (respectively 20,10,5 g.kg-1.d-1,ig). Except for the normal control group, each group was injected subcutaneously with morphine in a dose-escalating manner to establish a morphine-dependent model. On the 5th day of modeling, each group was given the corresponding drug, respectively, for 6 days. On the 8th day of modeling, each group was given naloxone (4 mg.kg-1, ip) to urge withdrawal and observe withdrawal symptoms and body weight changes within 2 h. Nitric acid reductase method was used to measure NO content and NOS activity in the homogenates of mouse brain. RESULTS: Compared with the model group, the jumping responses of the URWell group (20,10 g.kg-1.d-1) were significantly lower on the 8th and 9th days (P<0.05), clonidine group and URWell group (20, 10 g.kg-1.d-1) weight loss after withdrawal was significantly reduced in mice (P<0.05), NO content and NOS in the brain of clonidine and URWell (20 g.kg-1.d-1) mice. The activity decreased (P<0.05). CONCLUSION: URWell can inhibit morphine-dependent mice’s withdrawal symptoms, and its mechanism of action may be related to URWell’s effect on the NO/NOS system in the brain.