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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (5): 499-504.

• 研究原著 • 上一篇    下一篇

福尔马林所致炎性痛后脑内三种 COX亚型的变化及不同选择性 COX 抑制剂的镇痛效应比较

路志红, 熊晓云, 孟静茹, 刘振国, 王志鹏, 梅其炳   

  1. 第四军医大学药理教研室, 西安 710032, 陕西
  • 收稿日期:2005-02-23 接受日期:2005-04-06 出版日期:2005-05-26 发布日期:2020-11-19

Changes of three COX isoforms expression after formalin induced inflammatory pain in brain and analgesic effects of different COX inhibitors

LU Zhi-hong, XIONG Xiao-yun, MENG Jing-ru, LIU Zhen-guo, WANG Zhi-peng, MEI Qi-bing   

  1. Department of Pharmacology, Fourth Millitary Medical University, Xi'an 710032, Shaanxi, China
  • Received:2005-02-23 Accepted:2005-04-06 Online:2005-05-26 Published:2020-11-19
  • Contact: MEI Qi-bing, correspondence author, male, engaged in pharmacology. Tel:029-83374555   E-mail:deerlu@fmmu.edu.cn
  • About author:LU Zhi -hong, female, Ph.D, candidate, engaged in neuropharmacology.

摘要: 目的: 比较炎性痛后三种环氧合酶(cyclooxy-genase, COX) 亚型的表达变化, 以及选择性 COX 抑制剂不同应用方式对炎性痛的镇痛效应。方法: 小鼠足底注射福尔马林诱导炎性痛。用放射免疫分析及 RT-PCR分别评估脑COX-1、COX-2及 COX-3在福尔马林注射前、注射后 1、12 h、1、3、7、14、30、60 d 的变化。在镇痛效应的比较中, 动物被分成5 组 :对照组、SC 组、NS 组、IN 组及NS +SC 组。前 4组分别灌胃生理盐水、SC-560、NS-398 和 indomethacin。NS +SC 组在前一个月接受 NS-398, 后一个月接受 SC-560。测定各组动物在福尔马林注射前、注射后 1、12 h、1、3、7、14、30、60 d 的热痛阈。结果: COX-2 的表达在炎性痛后 12 h 到 3 d 升高显著, 而 COX-1 的表达在 2 周到 2 月升高显著。在整个观察时限内COX-3 的表达无明显变化。与其他组相比, NS +SC组动物的热痛阈在整个炎性痛过程中均明显提高。结论: 炎性痛后早期 COX-2 升高而晚期 COX-1 升高。COX-3 变化不明显。COX-1 抑制剂和 COX-2 抑制剂的结合使用比单纯使用其中一种能取得更好的镇痛效果。

关键词: 炎性痛, 环氧合酶, 环氧合酶抑制剂, 放射免疫分析, RT-PCR, 热板试验, 小鼠

Abstract: AIM: To compare the expression of three cyclooxygenase (COX) isoforms in the process of inflam-matory pain and evaluate the analgesic effects of different protocols about usage of COX inhibitors on inflammatory pain. METHODS: Formalinwas injected subplantarly to mice to induce inflammatory pain.The expression of COX-1, COX-2 and COX-3was evaluated by radioimmu-noassay and RT-PCR, respectively. For the analgesic ef-fect assay, animals were divided into 5 groups including control, SC, NS, IN and NS +SC group.The former 4 groups received saline, SC-560 (300μg°kg-1), NS-398 (150 μg°kg-1), and indomethacin (300μg°kg-1), re-spectively. In the NS +SC group, animals received NS-398 during the first 1 month and SC-560 during the sec-ond month in the NS +SC group.RESULTS: The ex-pression of COX-1was higher at the late phase while that of COX-2 was higher at the early phase of inflammatory pain.The expression of COX-3 did not significantly change in the process of inflammatory pain.Additionally, behavioral assessment showed that using COX-2 inhibitors at the early phase followed by COX-1inhibitors at the late phase could get better analgesic effect on inflammatory pain compared with single using COX-1 selective or COX-2 selective inhibitors. CONCLUSION: In brain, the ex-pression of COX-2 increases rapidly in the inflammatory pain processwhile COX-1 expression does not increase till the late phase. Brain COX-3 is poorly involved in the in-flammatory process.Combined use of COX-1 and COX-2 selective inhibitors may be a better protocol in inflamma-tory pain treatment.

Key words: inflammatory pain, cyclooxygenase COX inhibitor, radioimmunoassay, RT-PCR, hot plate CLC Number :R966