国际麻醉学与复苏杂志   2013, Issue (7): 4-4
    
改良尼古丁依赖-戒断大鼠模型的建立与疼痛敏感性观察
刘献文, 逯素芬, 于爱兰, 张宗旺1()
1.山东省聊城市人民医院
Establishment of modified nicotine dependence-withdrawal rat model and observation of pain sensitivity
 全文:
摘要：

目的：通过间断皮下注射尼古丁制作改良尼古丁依赖-戒断大鼠模型，观察尼古丁戒断后大鼠机械刺激缩足阈值（Mechanical withdrawal threshold，MWT）和热刺激缩足潜伏期（Thermal withdrawal latency，TWL）的变化。方法：SD大鼠30只，随机分成5组，每组6只，为正常对照组（Control组）、生理盐水组（NS组）、尼古丁3mg/kg/d组（NT3组）、尼古丁9mg/kg/d组（NT9组）和尼古丁18mg/kg/d组（NT18组），分别不注射、生理盐水、尼古丁1mg/kg、3mg/kg和6mg/kg皮下注射，3次/d，连续7d。于第7d末次注射后60min皮下注射美加明1mg/kg。观察大鼠注射尼古丁期间和戒断后体重变化、存活情况和尼古丁戒断评分。另外选取Control组、NS组和NT9组各6只大鼠，分别于注射生理盐水或尼古丁7d后测定右下肢足底MWT和TWL。结果：与NT3组比较，注射尼古丁后第7d，NT9组和NT18组大鼠体重增加缓慢（3.8±1.3g，2±0.3g vs 7.2±1.0g ）（P <0.05），戒断后第1d和第2d大鼠体重增加迅速（P <0.01），NT9组和NT18组大鼠美加明激发后出现更多的戒断症状（P <0.01），但NT18组大鼠死亡率达17%。与Control组比较，NT9组大鼠在尼古丁戒断后1～7dMWT明显降低（P <0.01），以第1d（36.5±1.9g）和第2d（37.5±0.9g）尤为显著（P <0.01）；TWL亦明显降低（P <0.01），以第4d（11.1±0.6s）最为显著（P <0.01）。结论：间断皮下注射尼古丁9mg/kg/d 7d可以成功制作改良尼古丁依赖-戒断大鼠模型，尼古丁戒断后大鼠疼痛敏感性增高。
关键词： 尼古丁，美加明，依赖，戒断，疼痛
Abstract:

Objective: To establish modified rat model of nicotine dependence-withdrawal syndrome by subcutaneous injection of nicotine, and observe mechanical withdrawal threshold（MWT） and thermal withdrawal latency(TWL) after nicotine withdrawal. Methods: 30 SD rats were randomly divided into 5 groups, 6 rats per group, including Control group, normal saline group (NS group), nicotine 3mg/kg/d group (NT3 group), nicotine 9mg/kg/d group (NT9 group) and nicotine 18mg/kg/d group (NT18 group). Each group received no injection, subcutaneous injection of normal saline, nicotine 1mg/kg, 3mg/kg and 6mg/kg respectively three times a day for seven days. At 60min after the last injection of nicotine, subcutaneous injection of mecamylamine 1mg/kg was given for each rat. Weight changes of rat during injections of nicotine and after nicotine withdrawal, survival rate and its withdrawal symptoms score were recorded. In addition, Control group, NS group and NT9 group were selected, 6 rats in each group。MWT and TWL were determined in the right hind paw during nicotine withdrawal. Results: Compared with NT3 group, on the seventh day after injection of nicotine, weight gain of the rats was significantly slow in NT9 group and NT18 group (3.8±1.3g，2±0.3g vs 7.2±1.0g） (P<0.05); on the first and the second withdrawal day, weight gain of the rats was significantly rapid in NT9 group and NT18 group (P<0.01). Compared with NT3 group, the rats in NT9 group and NT18 group had significant more withdrawal symptoms after mecamylamine precipitation (P<0.01). The incidence of mortality in NT18 group was 17%. Compared with control group, MWT in NT9 group had significantly decreased on the first day（36.5±1.9g）and the second day（37.5±0.9g）of nicotine withdrawal (P<0.01); TWL also significantly decreased on the fourth withdrawal day（11.1±0.6s）(P<0.01). Conclusion: By continuous subcutaneous injection of nicotine 9mg/kg/d for seven days, modified rat model of nicotine dependence-withdrawal syndrome can be successfully established. The pain sensitivity increased in rats with nicotine withdrawal.
Key words: nicotine, mecamylamine, dependence, withdrawal, nociception