超快速脱毒对吗啡成瘾大鼠血浆吗啡和脑组织β-内啡肽水平的影响  

Effects of ultrarapid opiate detoxification during general anesthesia on plasma morphine concentration and brain β-endorphin content in rats addicted to morphine

作　　者：唐昱英[1] 刘进[1] 罗南富[1] 廖大清[1] 

机构地区：[1]四川大学华西医院麻醉科

出　　处：《中华麻醉学杂志》2005年第10期755-758,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨超快速脱毒对吗啡成瘾大鼠血浆吗啡和脑组织β-内啡肽水平的影响。方法 Wistar雄性大鼠90只,随机分为正常组(n=5)、成瘾组(n=5)、自然戒断组(n=20)、单纯全麻组(n =20)、全麻+纳洛酮组(n=20)及可乐定处理组(n=20)。成瘾组、自然戒断组、单纯全麻组、全麻+ 纳洛酮组及可乐定处理组采用5日递增成瘾法建立大鼠吗啡成瘾模型。正常组和成瘾组在脱毒前取 血浆和脑组织,后四组分别在予以生理盐水、全麻、纳洛酮及可乐定等相应处理后,分别于脱毒后即 刻、脱毒后1、2、3 d处死5只大鼠,取血浆和脑组织,气相色谱／质谱法测定血浆吗啡浓度,放免法测定 脑组织p．内啡肽含量。结果成瘾组血浆吗啡浓度为(224±164)ng/ml,高于各脱毒组(P<0．01)。脱 毒后即刻,可乐定处理组血浆吗啡浓度高于各脱毒组(P<0．05);脱毒后1～3 d,各脱毒组血浆吗啡浓 度差异无统计学意义(P>0．05)。成瘾组脑组织β-内啡肽含量(18．7±4．2)ng/mg低于正常组(33．5± 3．8)ng/mg(P<0．01);脱毒后即刻,全麻+纳洛酮组和可乐定处理组脑组织β-内啡肽含量较正常组增 高(P<0．01),且脱毒后1～3 d均高于自然戒断组(P<0．05)。结论 超快速脱毒对吗啡成瘾大鼠脱 毒后3 d内血浆吗啡浓度没有影响,超快速脱毒的机制可能与纳洛酮和／(或)可乐定升高脑组织内源 性阿片肽有关。Objective To investigate the effects of ultrarapid opiate detoxification during general anesthesia on the plasma morphine concentration and brain β-endorphin content in rats addicted to morphine. Methods Ninety male Wistar rats aged 12-15 weeks weighing 180-220 g were randomized into 6 groups ： group Ⅰ normal animal （ n = 5） ; group Ⅱ morphine addiction （ n = 5） ; group Ⅲ natural withdrawal （ n = 20） ; group Ⅳ general anesthesia （ n = 20） ; group Ⅴ general anesthesia ＋ naloxone （ n = 20） and group Ⅵ clonidine pretreatment （ n = 20）, Morphine addiction was induced by subcutaneous injection of increasing doses of morphine sulphate for 5 days （5, 10, 20, 40 and 50 mg·kg^-1 t.i.d, x 5 days）. Morphine detoxification was started on the 6th day, General anesthesia was induced and maintained with γ-OH and midazolam i,m, supplemented with intermittent isoflurane inhalation to maintain loss of righting reflex. Spontaneous breathing was kept during general anesthesia. In group Ⅴ naloxone 0.05, 0.1 and 0.2 mg was injected subcutaneously at 5, 30 and 60 min after loss of righting reflex. Successful detoxification was defined as no withdrawal symptoms after subcutaneous injection of naloxone 0.1 mg. In groupl Ⅵ clonidine 0.05 mg·kg^-1 was given i.v. 1 hour before induction of anesthesia. Blood samples and brain tissue were obtained before detoxification in group Ⅰ （normal animal） and Ⅱ （morphine addiction） while in the other 4 groups they were obtained immediately and 1, 2, 3 day after detoxification. Results The plasma morphine concentration was 224 ＋ 164 ng·ml^-1 in group Ⅱ （ morphine addiction）, significantly higher than in all the detoxification groups （P 〈 0.05）. Plasma morphine concentration immediately after detoxification was significantly higher in clonidine pretreatment group （ Ⅵ ） than in the other 3 treatment groups （ Ⅲ, Ⅳ,Ⅴ ） （ P 〈 0.05）. However the difference disappeared gradually on the following three days. Bra

关 键 词：可乐定 阿片相关性障碍 麻醉 全身 吗啡依赖 脑 Β-内啡肽 

分 类 号：R749.6[医药卫生—神经病学与精神病学]