干旱区生态环境知识资源中心(Arid): 大鼠鞘内注射曲马多的抗伤害性效应及与脊髓alpha

Arid

	大鼠鞘内注射曲马多的抗伤害性效应及与脊髓alpha_2受体效应的关系
其他题名	The relationship between antinociceptive effect of intrathecal tramadol and the alpha_2-adrenoceptor effect of the
	刘克玄 1; 陈秉学 1; 黑子清 1; 黄文起 1; 卢汉平 2; 高锦辉 2; 李东菊 1
来源期刊	中华麻醉学杂志
ISSN	0254-1416
出版年	2003
卷号	23 期号:9 页码:696-699
中文摘要	目的探讨鞘内注射曲马多抗伤害性效应及与脊髓气受体效应的关系。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10mu组、育亨宾10mug组、育亨宾10mug+曲马多10mug 组、育亨宾10mug ＋纳洛酮10mug+曲马多10mug组。于大鼠左后爪掌心皮射2．5％福尔马林50mul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Dubulsson＆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一育亨宾为射性标记配基，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a_2 体结合的平衡解离常数（KD）及曲马多与与~3H- 育亨宾竞争结处受体的抑制常数（KI）。结果鞘内注人10mug的曲马多能显著抑制福尔马林注射后大鼠的疼痛反应。10mug育亨宾单独鞘内注人无明显抗伤害性效应（P ＞0．05），预处理可使10mug 曲马多鞘内注人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mug 预处理可使10mug 曲马多鞘内注人后大鼠的伤害效应评分增加200％。受体放射性分析表明，H一育亨宾的KD值为l．79nmouL，曲马多的Kl值为34．14mumol/L，IG-(50)为68．25mumol/L，提示曲马多翻吸受体的亲合力极低，约为育亨宾的l/l9000 。结论在脊髓水平，曲马多具有抗伤害性效应，抗伤害作用的一部分可能与其间接的脊髓a_2 体效应有关.
英文摘要	Objective To investigate the relationship between the antinociception of intrathecal tramadol and a2-adrenoceptor effect of the spinal cord in rats. Methods Forty adult Wistar rats of both sexes weighing 280-320 g were anesthetized with ketamine 40 mg·kg~(-1) and pentobarbital 20 mg~-1· kg~(-1)ip and PE-10 polyethylene catheter was placed in subarachnoid space 4-6 days before experiment. The animals were randomly divided into five groups of 8 animals : (1) control group received normal saline; (2) group T tramadol 10mug; (3) group Y yohimbine 10mug;group Y + T yohimbine 10mu+ tramacol 10mug and (5) group Y + N + T received yohimbine 10mug + naloxone 10mug + tramadol 10mug. The above-mentioned drugs including normal saline were injected intrathecally. 2.5% formalin 50mul 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 HC1 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 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 10mug could produce time-dependent antinociception. Yohimbine 10/tg alone did not produce antinociception ( P > 0.05), but pretreatment with yohimbine 10mug significantly reduced the antinociceptive effect of tramadol ( 10mug) at 35 min and 40 min and the nociception score increased by 56% and 41 % respectively ( P <0.01). Addition of naloxone increased the nociception score by 200% and 75% but the score was still lower than that in control group, but the difference was not statistically significant ( P > 0.05). Scatchard analysis of the saturation isotherms showed that3 H-yohimbine was bound to a single binding site with a Kd value of 1.79 nM. The competition curve of tramadol was sigmoidal with a Ki value of 34.14muM arid an IC50 value of 68.25muM. Tramadol was 19 000-fold less potent for binding to a_2-adrenoceptor oi the spinal cord as compared to H-yahimbine. Conclusion Intrathecal tramadol produces time-dependent antinociception. Tramadol has very low affinity with a2-adrenoceptor of the spinal cord. A part of its intrathecal antinociceptive effect was related to indirect a_2,-adrenoceptor effect of the spinal cord.
中文关键词	曲马朵 ; 注射，脊髓 ; 受体，肾上腺素能alpha2 ; 疼痛测定
英文关键词	Tramadol Injections, spinal Receptors,adrenergic,alphaa2 Pain measurement
语种	中文
国家	中国
收录类别	CSCD
WOS类目	SURGERY
WOS研究方向	Surgery
CSCD记录号	CSCD:1325873
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/204724
作者单位	1.中山大学附属第一医院麻醉科, 广州, 广东 510080, 中国; 2.中山大学实验核医学教研室, 广州, 广东 510080, 中国
推荐引用方式 GB/T 7714	刘克玄,陈秉学,黑子清,等. 大鼠鞘内注射曲马多的抗伤害性效应及与脊髓alpha_2受体效应的关系[J],2003,23(9):696-699.
APA	刘克玄.,陈秉学.,黑子清.,黄文起.,卢汉平.,...&李东菊.(2003).大鼠鞘内注射曲马多的抗伤害性效应及与脊髓alpha_2受体效应的关系.中华麻醉学杂志,23(9),696-699.
MLA	刘克玄,et al."大鼠鞘内注射曲马多的抗伤害性效应及与脊髓alpha_2受体效应的关系".中华麻醉学杂志 23.9(2003):696-699.