眼镜蛇毒活性成分对神经病理性疼痛模型大鼠的镇痛作用及K_(ATP)通道阻滞药对其的影响研究

Study on Antinociceptive Effects of Snake Venom Analgesic Fraction from Naja Tripudians on Neuropathic Pain Model Rats and Effects of ATP-sensitive K^+ Channels Inhibitors on It

目的:研究鞘内注射眼镜蛇毒活性成分(AF)对病理性疼痛模型大鼠的镇痛作用,及三磷酸腺苷(ATP)敏感钾(KATP)通道阻滞药对其的影响。方法:采用左侧腰5脊神经结扎并切断,建立神经病理性疼痛模型大鼠;采用鞘内注射方法,考察给予不同剂量(0、0.02、0.04、0.08mg.kg-1)AF后24h内模型大鼠双侧后足的50%机械性撤足反应阈值(PWT)。另将模型大鼠分为对照组、格列苯脲(5mg.kg-1)组、AF(0.04mg.kg-1)组及其联用组,考察各组大鼠给药后24h内双侧后足的50%PWT。结果:与给药前比较,给药后0.5～24h时段0.08mg.kg-1AF组大鼠的50%PWT明显增加(P<0.05),给药后1～6h时段0.04mg.kg-1AF组大鼠的50%PWT明显增加(P<0.05),给药后2～6h时段3个AF剂量组大鼠的50%PWT明显增加(P<0.05);与对照组比较,格列苯脲组50%PWT无明显变化,AF组1～6h时段50%PWT明显增加(P<0.05);与AF组比较,联用组给药后1～6h时段50%PWT明显减少(P<0.05),且手术同侧后足与对侧后足比较无明显差异。结论:鞘内注射AF可缓解外周神经损伤引起的神经病理性疼痛,KATP通道阻滞药可完全阻断其镇痛作用。

OBJECTIVE：To investigate the antinociceptive effect of intrathecal injection of snake venom analgesic fraction（AF） isolated from Naja tripudians on the neuropathic pain model rats,and to explore the effects of ATP-sensitive K＋ channel inhibitors on antinociceptive effect of AF.METHODS：L5 of left spinal nerve ligation and ectomy were conducted to establish neuropathic pain model rats.50% paw withdrawal threshold（PWT） of bilateral hindfoot in model rats were determined within 24 h after different intrathecal dose of AF（0,0.02,0.04,0.08 mg·kg-1）.Model rats were divided into control group,glybenclamide group（5 mg·kg-1）,AF group（0.04 mg·kg-1） and drug combination group,and 50% PWT of bilateral hindfoot in those rats within 24 h after medication was investigated.RESULTS：Compared with before medication,50% PWT of rats during 0.5 to 24 h after given 0.08 mg·kg-1 AF increased significantly（P〈0.05）,50% PWT of rats during 1 to 6 h after given 0.04 mg·kg-1AF increased significantly（P〈0.05）,50% PWT of rats during 2 to 6 h after given AF increased significantly（P〈0.05）;compared with control group,50% PWT of rats in glybenclamide group had no significant change,50% PWT of rats in AF groups during 1 to 6 h after medication increased significantly（P〈0.05）;compared with AF group,50% PWT of rats in drug combination group during 1 to 6 h after medication decreased significantly（P〈0.05）,and ipsilateral hindfoot wasn’t significantly different from offside hindfoot.CONCLUSION：Intrathecal injection of AF could relieve the neuropathic pain induced by peripheral nerve injury,and ATP-sensitive K＋ channel inhibitors can block antinociceptive effect of AF completely.