利扎曲普坦对硝酸甘油型偏头痛模型大鼠行为学和外周血中疼痛相关因子水平的影响

Effects of rizatriptan on behavior and pain-related cytokines in peripheral blood of rat models with nitroglycerin-type migraine

目的：观察利扎曲普坦对偏头痛模型大鼠行为学和外周血中疼痛相关因子的影响，探讨曲普坦类药物对偏头痛的治疗作用。方法：24只健康 Wistar大鼠随机分为空白对照组、偏头痛组、利扎曲普坦对照组和利扎曲普坦治疗组，每组6只。利扎曲普坦对照组和利扎曲普坦治疗组大鼠给予利扎曲普坦灌胃，剂量为1 mg·kg-1·d-1（药物剂量根据成人常规每日口服剂量进行换算），空白对照组和偏头痛组大鼠给予生理盐水灌胃（1 mL·d-1）。各组大鼠连续灌胃给药7 d后，偏头痛组和利扎曲普坦治疗组大鼠制备硝酸甘油型偏头痛动物模型，空白对照组和利扎曲普坦对照组给予同剂量生理盐水，记录各组大鼠给予药物（硝酸甘油注射剂/生理盐水）后60～90 min行为学表现；2 h后处死大鼠，留取外周血，检测各组大鼠血清降钙素基因相关肽（CGRP）、5-羟色胺（5-HT）、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平。结果：与偏头痛组比较，利扎曲普坦治疗组大鼠行为学评分明显降低（P＜0.05）。与空白对照组比较，偏头痛组大鼠外周血中 CGRP水平明显升高（P＜0.05）；偏头痛组大鼠外周血中5-HT水平降低，但差异无统计学意义（P＞0.05）；与空白对照组比较，利扎曲普坦对照组大鼠外周血中5-HT水平明显升高（P＜0.05）；与偏头痛组比较，利扎曲普坦治疗组大鼠外周血中5-HT水平明显升高（P＜0.05）；各组大鼠外周血中 IL-1β和 TNF-α水平无明显差异（P＞0.05）。结论：利扎曲普坦能够减轻硝酸甘油型偏头痛模型大鼠行为学症状，使偏头痛大鼠头痛发作期外周血中5-HT水平升高，改善偏头痛发作时血管舒缩功能紊乱的状态，减轻因5-HT耗竭而引起的血管过度扩张。

Objective To observe the influence of rizatriptan on the behavior and pain-related cytokines in peripheral blood of the migraine model rats, and to investigate the theraputic effect of rizatriptan on migraine.Methods A total of 24 rats were randomly divided into：control group,migraine group,rizatriptan control group and rizatriptan treatment group.The rats in rizatriptan control and rizatriptan treatment groups were intragastrically perfused with rizatriptan,1 mg＆#183;kg-1 per day （according to the adult daily dose）,and the rats in control and migraine groups were perfused with normal saline,1 mL per day. After 7 d, nitroglycerin was subcutaneously inj ected into the buttocks of the rats in rizatriptan treatment and migraine groups to induce migraine.Normal saline was injected into the rats in control and rizatriptan control groups.At 60-90 min following nitroglycerin injection,the total number of behavioral symptoms was measured.The serum calcitonin gene-related peptide（CGRP）,5-hydroxytryptamine （5-HT ）, interleukin-1β（IL-1β）, and tumor necrosis factor-α（TNF-α） levels were determined using ELISA. Results Compared with migraine group, the behavioral score of the rats in rizatriptan treatment group was significantly decreased （P〈0.05）.The serum CGRP level of the rats in migraine group was significantly higher than that in control group （P〈0.05）.Compared with control group,the serum 5-HT level of the rats in and migraine group was decreased, but there was no significant differece （P〉0.05 ）;the serum 5-HT level in rizatriptan control group was significantly increased（P〈0.05）.The serum 5-HT level of the rats in rizatriptan treatment group was significantly increased compared with migraine group （P〈0.05）.The serum IL-1βand TNF-αlevels of the rats in varions groups had no significant differences （P〉0.05）.Conclusion Rizatriptan can relieve the behavior symptoms in nitroglycerin-induced migraine model rats, increase the serum 5-HT level, improve the vasomotor disturbance,and relieve the angiectasis.