蛋白激酶C的脊髓作用对局麻药外周神经阻滞耐药反应的影响

Spinal action of protein kinase C influences tachyphylaxis to peripheral local anesthetic nerve block

目的 探讨蛋白激酶C(proteinkinaseC ,PKC)在脊髓的作用与局麻药外周神经阻滞耐药的关系。方法 将 45只长期蛛网膜下腔置管大鼠随机分为 5组 ,分别接受蛛网膜下腔注射生理盐水 ,蛋白激酶C抑制剂GM1神经节苷酯 (GM1ganglioside) 160nmol或 5 0 0nmol,或蛋白激酶C抑制剂白屈菜季铵碱 (chelerythrine) 160nmol或 5 0 0nmol (n =9)。10min后用 3 %氯普鲁卡因 0 .3ml依次 3次阻滞大鼠坐骨神经 ,用热板、触觉复位、单足跳和肌力测试记录阻滞时间。结果 蛋白激酶C抑制剂GM1神经节苷酯和白屈菜季铵碱在低剂量 160nmol对局麻药耐药反应无显著影响 ,但是在高剂量 5 0 0nmol两个药物都可显著抑制局麻药耐药的程度。结论 大鼠蛋白激酶C可以通过脊髓作用抑制局麻药外周神经阻滞的耐药反应的发生。

Objective To test the hypothesis that spinal protein kinase C mediates tachyphylaxis to local anesthetic peripheral nerve block. Methods 45 rats were implanted chronically an intrathecal catheter. 9 rats in each groups received blinded intrathecal injection of saline or 160 nmol or 500 nmol of protein kinase C inhibitor GM1 ganglioside, 160 nmol or 500 nmol of protein kinase inhibitor chelerrythrine. Three sequential sciatic nerve blocks were performed with 0.3 ml of 3% 2-chloroprocaine 10 min later. Duration of block was recorded with hot-plate, tactile placing, right response and motor strength tests. Results The spinal action of protein kinase C inhibitors at low dose of 160 nmol administered intrathecally had no significant effect on local anesthetic tachyphylaxis, but thachyphylaxis was significantly reduced at high dose of 500 nmol of protein kinase C inhibitor GM1 ganglioside or chelerythrine ( P <0.05). Conclusion Spinal action of protein kinase C inhibitor prevents tachyphylaxis to local anesthetic block.