吗啡镇痛耐受大鼠中脑导水管周围灰质μ受体和δ受体协同表达下调  

DOWN-REGULATION OF PERIAQUEDUCTAL GRAY μ AND δ OPIOID RECEPTOR CO-EXPRESSION IN MORPHINE ANTINOCICEPTIVE TOLERANT RATS

作　　者：李玄英[1] 孙莉[1] 刘晓艳[1] 刘若杉[1] 徐磊[1] 王猛[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院麻醉科,北京100021

出　　处：《中国药物依赖性杂志》2009年第1期13-20,共8页Chinese Journal of Drug Dependence

基　　金：首都医学发展基金重点项目(2005-2057)资助

摘　　要：目的:测定吗啡镇痛耐受大鼠中脑导水管周围灰质(PAG)中μ受体和δ受体mRNA和蛋白表达的变化,以进一步探索吗啡耐受的发生机制。方法:健康成年♂Wistar大鼠32只,随机平均分为生理盐水对照组(NS组,n=16)和吗啡组(MS组,n=16)。采用盲法进行给药和疼痛行为测定。每天早、晚两次皮下注射(sc)药物并于上午注射前、后30 min测定大鼠的热甩尾潜伏期(TFL)作为痛阈指标。NS组和MS组分别sc生理盐水1 ml·kg-1和吗啡10 mg·kg-1,连续注射7 d,d8早晨各组分别取8只处死,剩余大鼠(分别记为NSN组和MSN组)d8早、晚两次sc纳洛酮0.4 mg·kg-1,并在d9处死。以TFL恢复至基础水平作为出现吗啡耐受的标准。采用免疫组织化学染色方法和实时定量PCR法分别检测PAG中μ和δ受体的蛋白表达和mRNA表达。结果:观察期两组大鼠的体重增加量在组间差异无显著性。两组大鼠每天注射前测定的TFL差异无显著性。MS组在d1 sc吗啡后TFL明显升高(P<0.05);在d2应用吗啡后,TFL升高达到最高值,且明显高于d1用药后水平(P<0.05),随后该组应用吗啡后的TFL逐渐降低,直至d7用药后TFL降至基础水平(P>0.05)。应用纳洛酮后,MSN亚组的TFL与NS组、NSN亚组以及基础值相比差异无显著性。连续应用吗啡7 d后,MS组PAG中μ和δ受体的蛋白表达和mRNA表达均较NS组显著降低(P<0.05)。结论:PAG中μ受体和δ受体共同参与了吗啡耐受机制,而且吗啡耐受大鼠PAG中μ受体和δ受体发生了协同表达下调。Objective：To evaluate the changes of μ and δ opioid receptor in periaqueductal gray（PAG） of morphine antinociceptive tolerant rats,and to further explore the mechanisms of morphine antinociceptive tolerance.Methods：Thirty two adult male Wistar rats were randomly allocated equally to Group NS（n=16）,which received a subcutaneous injection（sc）of 1 ml·kg-1 normal saline in the nape,and Group MS（n=16）,which received an injection（sc） of morphine 10 mg·kg-1.All rats were housed in the same environment and received injection twice a day for 7 days.In the morning of the 8th day,8 control rats and 8 morphine rats were killed.The remaining rats,which named as NSN subgroup and MSN subgroup,respectively,received no further morphine injections,but received 2 injections of naloxone（0.4 mg·kg-1） on the 8th day,and were killed in the morning of the 9th day.The hot water tail-flick latency（TFL） was measured 30 min before and after every morning injection,as an index of pain threshold.Morphine tolerance was developed as TFL returned to the baseline level.The expression of μ and δ opioid receptor in PAG was analyzed by IHC and real time PCR,respectively.Results：The rats＇ weight gain in the two groups during the observation period was not significantly different.The pain behaviors indicated that TFLs before injection every morning were not different significantly in the two groups.The pain threshold of Group MS increased significantly after the first morphine injection（P〈0.05） and reached the highest value on the second day,which was much higher than the first day value（P〈0.05）.But as injection increasing,the average pain threshold after injection in Group MS shortened gradually and returned to baseline value after 7 day injection.There was no significant difference in TFL after naloxone injection between groups and compared with the baseline value.After 7 day injection,the protein expression and mRNA expression of PAG μ and δ opioid receptor in Group MS decreased significantl

关 键 词：吗啡耐受 中脑导水管周围灰质 Μ受体 Δ受体 下调 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R614.42[医药卫生—基础医学]