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【摘要】 探讨蛛网膜下腔(鞘内)七叶皂苷及混合可乐定对甲醛炎症痛的治疗作用。【方法】 雄性SD大鼠(250 ～ 300 g)随机分为对照组、七叶皂苷组、可乐定组、混合药物组、拮抗组。蛛网膜下腔置管后注射实验药物，制作甲醛炎症痛模型，观察大鼠行为学改变情况，记录60 min内每5 min的退缩反应时间(s)，采用线性回归的方法计算各药物的半数有效剂量(ED50)及其95%可信区间(CI95)，用等辐射法评价药物的相互作用。【结果】 鞘内单独注射七叶皂苷或可乐定可产生剂量依赖性的抗炎症痛作用;鞘内七叶皂苷和可乐定混合，可以产生明显的协同效应;鞘内育亨宾预处理不能拮抗鞘内七叶皂苷的抗炎症痛作用，而可乐定及七叶皂苷混合可乐定的抗炎症痛作用可被育亨宾拮抗或部分拮抗。【结论】 鞘内单独注射七叶皂苷或可乐定可产生剂量依赖性抗炎症痛作用;鞘内注射七叶皂苷能增强可乐定的抗炎症痛作用医.学.全.在.线www.med126.com。
【关键词】 甲醛; 炎症痛; 七叶皂苷; 可乐定; 大鼠
Synergistic Effects between Intrathecal Escin and Clonidine on Treatmentf Inflammatory Pain in Rats LI Qiang， OUYANG Han-dong， HE Wei-xiong， ZENG Wei-an 1. Guangzhou Medical College Cancer Hospital， Guangzhou， 510095; 2. State Key Laboratory of Oncology in SouthernSun Yat-sen University Cancer Center， Guangzhou 510060， ChinaAbstract： 【Objective】 To investigate the effects of intrathecal escin and its interaction with clonidine on treatment of inflammatory pain induced by formaldehyde injection. 【Methods】 Male SD rats weighing 250 ～ 300 g were implanted with chronic lumbar intrathecal catheters， and were randomly divided into： group control; group escin; group clonidine; group escin + clonidine and group yohimbine (pretreatment with intrathecal yohimbine before intrathecal administration of escin， clonidine and a mixture of escin and clonidine). The formaldehyde test was used as a model of nociception. Antinociceptive effect was assessed by Biphasic painful behavior (flinch time per 5 min). The dose-response lines were fitted using linear regression analysis， and ED50 values and their 95% confidence intervals (CI95) were calculated. Isobolographic analysis of the escin and clonidine interaction was conducted. 【Result】 Intrathecal escin dose-dependently suppressed the flinch during phase Ⅱ in formaldehyde test. The ED50 of escin alone was 16.71 μg in phase Ⅱ. Intrathecal clonidine produced dose-dependent suppression of the biphasic responses in formaldehyde test. The ED50 of clonidine alone was 4.17 μg in phase Ⅰ and 2.58 μg in phase Ⅱ. Isobolographic analysis showed that the combination of intrathecal escin and clonidine synergistically reduced flinching activity in phase Ⅱ. The experimental ED50 of combination was significantly lower than the theoretical ED50. Intrathecal pretreatment with yohimbine attenuated the effects of clonidine and the combination of escin and clonidine， but antinociception of escin cannot be antagonized by pretreatment of yohimbine. 【Conclusion】 Intathecal escin and clonidine alone produced a dose-dependent treatment effects on inflammatory pain. The enhancing effects were found between intrathecal escin and clonidine.
Key words： formaldehyde; inflammatory pain; escin; clonidine; rats
炎症痛在临床广泛存在，目前常用非甾体类抗炎镇痛药(NSAID)或阿片类药物进行治疗，但NSAID 类的消化道不良反应及心血管风险限制了它们的应用[1-2]。而阿片类药物的便秘、药物耐受情况在长期用药时发生率极高。因此，临床迫切需要抗炎症痛新药及协同治疗方法。七叶皂苷(Escin)属三萜皂苷类化合物，具有抗炎、抗水肿及增加静脉张力的作用[3]，但是否具有抗炎症痛作用未见报道。本研究通过制作大鼠甲醛炎症痛蛛网膜下腔(鞘内)给药模型，评价了七叶皂苷及混合可乐定的抗炎症痛作用医.学.全.在.线www.med126.com。
