神经元型一氧化氮合酶抑制药增强氯胺酮的麻醉作用

目的　应用神经元型一氧化氮合酶 (nNOS)抑制药 7 硝基吲唑 (7 NI) ,探讨一氧化氮(NO)在氯胺酮麻醉作用机制中的意义。方法　 70只雄性昆明小鼠随机分七组 ,每组 10只。Ⅰ组 :生理盐水 10ml/kg ;Ⅱ组 :花生油 10ml/kg ;Ⅲ组 :7 NI 10mg/kg ;Ⅳ组 :7 NI 30mg/kg ;Ⅴ组 :7 NI6 0mg/kg ;Ⅵ组 :L 精氨酸 (L Arg) 5 0 0mg/kg ;Ⅶ组 :7 NI 6 0mg/kg +L Arg5 0 0mg/kg。均经腹腔注射 ,30分钟后再腹腔注射氯胺酮 10 0mg/kg。观察每只小鼠翻正反射消失 (LRR)开始和持续时间。 结果　 10mg/kg7 NI对LRR持续时间无明显影响 (P >0 0 5 )。 30mg/kg、6 0mg/kg7 NI可使LRR持续时间显著延长 ,L Arg5 0 0mg/kg显著缩短LRR持续时间 (P <0 0 1)。同时给予 5 0 0mg/kgL Arg和6 0mg/kg7 NI能逆转 7 NI对LRR的影响。结论　抑制nNOS活性能增强氯胺酮的麻醉作用 ,提示中枢NO信息途径可能在氯胺酮麻醉的分子机理中起作用。

Neuronal nitric oxide synthase inhibitor,7-nitro indazole,enhances ketamine anaesthesia

Objective To investigate the enhancement effect of 7-nitroindazole （7-NI） on ketamine anesthesia．Methods Seventy male Kunming mice were divided randomly into seven groups．The mice were pre-administered intraperitoneally（ip） saline 10ml／kg、arachis oil 10 ml／kg、7-NI 10mg／kg、7-NI 30ml／kg、7-NI 60mg／kg、L-arginine 500mg／kg or 7-NI 60mg／kg plus L-arginine 500mg／kg respeetively 30min before ipketamine 100mg／kg．Anaesthesia was defined as loss of righting reflex （LRR） for 10seconds．The onset and duration of LRR were recorded．Results There were no significant changes in the onset of LRR in all groups．7-NI increased the LRR duration in a dose-dependent manner．10mg／kg 7-NI did not alter LRR duration significantly whereas at doses of 30mg／kg and 60mg／kg a significant prolongation of LRR duration was observed．L-arginine pretreatment significantly shortened the LRR duration（P＜0.01）．Combined treatment with 7-NI 60 mg／kg and L-arginine 500mg／kg blocked the effects of 7-NI on LRR duration times．Conclusions Acute inhibition of nNOS by 7-NI results in a longer duration of ketamine anaesthesia．The results support the assumption that the NO signal pathway may be involved in the mechanism of ketamine anaesthesia．