大鼠鞘内注射曲马多的抗伤害性效应及与脊髓α_2受体效应的关系  

The relationship between antinociceptive effect of intrathecal tramadol and the a2-adrenoccptor effect of the spinal cord in rats

作　　者：刘克玄[1] 陈秉学[1] 黑子清[1] 黄文起[1] 卢汉平[2] 高锦辉[2] 李冬菊[1] 

机构地区：[1]中山大学附属第一医院麻醉科,广州市510080 [2]中山大学实验核医学教研窒,广州市510080

出　　处：《中华麻醉学杂志》2003年第9期696-699,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨鞘内注射曲马多抗伤害性效应及与脊髓α2受体效应的关系.方法Wistar大鼠蛛网膜下腔埋管后随机分为5组(n=8):生理盐水对照组、曲马多10μg组、育亨宾10μg组、育亨宾10 μg+曲马多10μg组、育亨宾10μg+纳洛酮10μg+曲马多10μg组.于大鼠左后爪掌心皮下注射2.5%福尔马林50μl后鞘内注入上述药物,从福尔马林注射后的30 min开始对大鼠的表现行为进行Dubuisson & Dennis评分.另取一组大鼠断头处死后取腰段脊髓制成细胞膜悬液,以3H-育亨宾为放射性标记配基,盐酸育亨宾为非标记配基,曲马多为竞争剂,行标记配基的饱和结合反应及竞争取代反应,并计算3H-育亨宾与脊髓α2受体结合的平衡解离常数(KD)及曲马多与3H-育亨宾竞争结合脊髓α2受体的抑制常数(KI).结果鞘内注入10μg的曲马多能显著抑制福尔马林注射后大鼠的疼痛反应.10μg育亨宾单独鞘内注入无明显抗伤害性效应(P＞0.05),预处理可使10μg曲马多鞘内注入后大鼠的伤害效应评分最多可增加56%,但仍低于对照组大鼠的伤害性效应评分(P＜0.05);增加纳洛酮10μg预处理可使10μg曲马多鞘内注入后大鼠的伤害效应评分增加200%.受体放射性分析表明3H-育亨宾的KD值为1.79 nmol/L,曲马多的KI值为34.14μmol/L,IC50为68.25μmol/L,提示曲马多与脊髓α2受体的亲合力极低,约为育亨宾的1/19 000.结论在脊髓水平,曲马多具有抗伤害性效应,其抗伤害作用的一部分可能与其间接的脊髓α2受体效应有关.Objective To investigate the relationship between the antinociception of intrathecal tramadol and Oh -adrenoceptor effect of the spinal cord in rats. Methods Forty adult Wistar rats of both sexes weighing 280-320 g wen- anesthetized with ketamine 40 mg . kg-1 and pentobarbital 20 mg. kg-1 ip and PE-10 polyethylene catheter was placed in subarachnoid space 4-6 days before experiment. Tbe animals were randomly divided into live groups of 8 animals : (1) control group received normal saline; (2) group T tramadol 10 μg; (3) group Y yohimbine 10μg;group Y + T yohimbine 10 μg + tramacol 10 μg and (5) group Y + N + T received yohimbine 10 μg + naloxone 10μg + tramadol 10 μg. The above-mentioned drugs including normal saline were injected intrathecally. 2.5% formalin 50ul was injected subcutaneously into the plantar region of left hindpaw. 15 min later the above-mentioned drugs were injected intrathecally. In group 4 and 5 yohimbine and naloxone were given 5 min before tramadol. The animals were placed in a 30 cm × 30 cm× 30 cm glass box for evaluation of pain behavior, which was graded from 0 ( no pain) to 3 ( severe Pain) according to Dobuisson and Dennis. Another sixteen animals were decapitated and lumbar spinal cord was rapidly removed and made into crude membrane suspension. H-yohimbine was used as radioligand for specific binding, yohimbin HCl for nonspecific binding and tramadol as competitor. Drug displacement studies for specific H-yohimbine binding were carried out under standard incubation conditions with 0.21 nmol.L-1 to 2. 1 nmol.L-1 (10 concentrations) of tramadol. Dissociation constant (Kd) and inhibition constant ( Ki) were obtained by special computerized parameter estimation method program. Results Intrathecal tramadol 10 μg could produce time-dependent antinociception. Yohimbine 10μg alone did not produce antinociception ( P > 0.05), but pretreatment with yohimbine 10 ug significantly reduced the antinociceptive effect of tramadol ( 10ug) at 35 min and 40 min and the nociception score incre

关 键 词：大鼠 鞘内注射 曲马多 抗伤害性效应 脊髓α2受体 

分 类 号：R96[医药卫生—药理学]