瞬时受体电位离子通道A1对慢性偏头痛大鼠模型的作用及氟桂利嗪对其影响

The role of Transient receptor potential ion channel A1 in chronic migraine rat model and the effect of flunarizine

目的本实验通过炎性汤(IS)反复刺激大鼠上矢状窦区硬脑膜疼痛感受器建立慢性偏头痛(CM)大鼠模型,研究瞬时受体电位离子通道A1(TRPA1)及降钙素基因相关肽(CGRP)在CM大鼠模型中的作用,探讨TRPA1在CM发生发展中的可能作用及氟桂利嗪对其影响。方法清洁级SD雄性大鼠48只,体重250~300 g,按随机数字法分为4组(n=12):正常对照组(A组)、假手术组(B组)、CM模型组(C组)及药物干预组(D组)。注射试剂1 h后安静环境中进行大鼠行为学观察及机械刺激缩足反应阈值(PWMT)测定。采用Elisa、Real-Time PCR及Western-Blot技术检测大鼠硬脑膜、三叉神经节(TG)及三叉神经脊束核尾核(TNC)组织部位TRPA1及CGRP表达情况。结果与A组、B组相比较,C组大鼠行为学评分明显升高,PWMT测定值降低,大鼠硬脑膜、TG及TNC组织部位中CGRP及TRPA1表达量均明显上调,差异有统计学意义(P<0.05);与C组相比较,D组大鼠行为学评分降低,PWMT测定值升高,硬脑膜、TG及TNC组织部位CGRP及TRPA1表达量均下调,差异有统计学意义(P<0.05)。结论 I TRPA1受体可能参与CM发作的病理生理过程;氟桂利嗪可能通过影响TRPA1受体表达,引起CGRP表达下调,从而缓解CM症状。

Objective A chronic animal model of migraine was established through repeated stimulation of the superior sagittal sinus of SD rats with inflammatory Soup （IS） in this study. By discussing the role of TRPA1 and CGRP in the model of chronic migraine rats,exploring the possible role of TRPA1 in the development of CM and the influence of fluoridiazine hydrochloride. Methods Forty-eight SD male rats,weight 250-300g,were randomly divided into four groups（ n =12）：normal group（A group）、sham operation group（B group）、CM group（C group） and drug intervention group（D group）. After injection of reagent 1 h start behavior evaluation and PWMT assessment. Also,the Elisa、Real-Time PCR and Western-Blot techniques were used to detect the expression of the CGRP and TRPA1 in the dura mater、TG and TNC. Results Compared with A、B group,the behavior score of C group increased significantly and PWMT measurements is was reduced,the expression of CGRP and TRPA1 were obviously raised in the dura mater、TG and TNC （P〈0.05）;Compared with C group,the expression of CGRP and TRPA1 were decreased（P〈0.05）. Conclusion TRPA1 receptor may participate in the development of CM and play its role in CM. Flunarizine Hydrochloride Capsules may induce CGRP expression by inhibiting the expression of TRPA1 receptor,which can alleviate migraine attacks.