吗啡耐受大鼠脊髓NR2B与mGluR5的相互作用  

Interaction between NMDA receptor subunit 2B and metabotropic glutamate receptor 5 in the spinal cord of morphine-tolerant rats

作　　者：江伟[1] 刘金变[1] 严海[1] 

机构地区：[1]上海交通大学附属第六人民医院麻醉科,200233

出　　处：《中华麻醉学杂志》2009年第2期136-139,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价吗啡耐受大鼠脊髓含2B亚基的NMDA受体（NR2B）和代谢型谷氨酸受体5（mGluR5）的相互作用。方法雄性SD大鼠，体重220～280g，取鞘内置管成功的大鼠16只，随机分为2组（n=8），对照组（C组）鞘内注射生理盐水10μl；吗啡组（M组）鞘内注射吗啡10μg（10μl）。每日给药2次，连续7d。于给药前和给药后30min采用热水缩尾法测定痛阈，计算最大镇痛效应百分比（MPE）。最后1次痛阈测定结束后第2天，处死大鼠，取4-5，脊髓背角，采用Westernblot法测定NR2B和mGluR5蛋白表达水平；应用免疫共沉淀技术，NR2B抗体沉淀提取蛋白，Western blot法检测沉淀物。结果与C组比较，给药1～5d时M组MPE升高（P〈0．01），给药7d时差异无统计学意义（P〉0．05）。与C组比较，M组NR2B蛋白表达差异无统计学意义（P〉0．05），mGluR5蛋白表达上调（P〈0．01）。免疫共沉淀法证实NR2B与mGluR5存在相互作用。结论吗啡耐受大鼠脊髓NR2B与mGluR5存在相互作用。Objective To investigate the interaction between NMDA receptor snbunit 2B （NR2B） and metabotropie glutamate receptor 5 （mGluR5） in the spinal cord of morphine-tolerant rats. Methods Sixteen male SD rats weighing 220-280 g were randomly divided into 2 groups with 8 rats in each group： control group （C） and morphine group （M）. In group M morphine 10 μg was administered intrathecally （IT） twice a day for 7 consecutive days. In group C equal volume of normal saline was given instead of morphine. Tail flick latency （TFL） （a segment of tail 4-5 em long was immersed in 52-53 ℃ hot water） was used to measure the antinociceptive effect of morphine before and 30 min after morphine administration every morning. MPE （percentage of maximal possible effect） was calculated （pain threshold after drug administration - baseline pain threshold）/（ 10 - baseline pain threshold） × 100% . The animals were killed at the next day after last IT administration and the dorsal half of L4,5 spinal cord was isolated and homogenized for determination of NR2B and mGluR5 protein expression by Western blot and CO-IP. Results MPE was significantly inereased at 1-5 d of drug administration and returned to baseline at 7 d in group M as compared with group C. The mGluR5 protein expression was significantly upregulated in group M as compared with group C but there was no significant difference in NR2B protein expression between the 2 groups. Conclusion There is interaction between NR2B and mGluR5 in the spinal cord of morphine-tolerant rats.

关 键 词：吗啡 药物耐受 脊髓 受体 N-甲基-D-天冬氨酸 受体 谷氨酸 

分 类 号：R96[医药卫生—药理学]