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目的:比较炎性痛后三种环氧合酶(cyclooxygenase,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RTPCR分别评估脑COX1、COX2及COX3在福尔马林注射前、注射后1、12h、1、3、7、14、30、60d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、SC560、NS398和indomethacin。NS+SC组在前一个月接受NS398,后一个月接受SC560。测定各组动物在福尔马林注射前、注射后1、12h、1、3、7、14、30、60d的热痛阈。结果:COX2的表达在炎性痛后12h到3d升高显著,而COX1的表达在2周到2月升高显著。在整个观察时限内COX3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COX2升高而晚期COX1升高。COX3变化不明显。COX1抑制剂和COX2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。
OBJECTIVE: To compare the changes of three cyclooxygenase (COX) subtypes after inflammatory pain and the analgesic effects of different COX inhibitors on inflammatory pain. Methods: The mice were injected with formalin to induce inflammatory pain. Radioimmunoassay and RTPCR were used to evaluate the changes of brain COX1, COX2 and COX3 before, 1, 12, 13, 30, 30 and 60 days after injection. In the analgesic effect comparison, animals were divided into 5 groups: control group, SC group, NS group, IN group and NS + SC group. The first four groups were given normal saline, SC560, NS398 and indomethacin respectively. The NS + SC group received NS398 the previous month and the SC560 the following month. The heat pain threshold of each group before and after 1, 2, 3, 7, 14, 30 and 60 days after injection was measured. Results: The expression of COX2 increased significantly from 12h to 3d after inflammatory pain, while the expression of COX1 increased significantly from 2 weeks to 2 months. COX3 expression did not change significantly over the entire observation period. Compared with the other groups, the heat pain threshold in NS + SC animals was significantly increased throughout the inflammatory pain. CONCLUSION: COX2 increased early after inflammatory pain and increased COX1 late. COX3 change is not obvious. The combination of COX1 inhibitors and COX2 inhibitors results in better analgesic effects than either alone.