天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (12): 2180-2186.doi: 10.16333/j.1001-6880.2018.12.023

• 开发研究 • 上一篇    下一篇

新型天麻素衍生物在辣椒碱致大鼠偏头痛模型中的疗效

谷漫峡1,王平汉1,陈雏2,杜俊蓉1*   

  1. 1四川大学华西药学院,成都 610041;2四川省中医药科学院,成都 610041
  • 出版日期:2019-01-02 发布日期:2019-01-02

Curative Effect of A Novel Gastrodin Derivative on Capsaicin-Induced Migraine in Rats

GU Man-xia1, WANG Ping-han1, CHEN Chu2, DU Jun-rong1*   

  1. 1West China School of Pharmacy,Sichuan University,Chengdu,610041,China;2Sichuan Academy of Chinese Medicine Sciences,Chengdu,610041,China
  • Online:2019-01-02 Published:2019-01-02

摘要: 辣椒碱是辣椒属植物的活性成分,主要作用于C型感觉神经元和外周神经轴突,可触发某些类型的疼痛反应。本研究观察了新型天麻素衍生物在辣椒碱所致的大鼠偏头痛模型中的疗效,采用小脑延髓池注入辣椒碱的方法造大鼠急性偏头痛模型,并在造模前1 h 灌胃给予溶媒、Gas(天麻素,50 mg/kg,100 mg/kg)、Gas-D(天麻素衍生物,50 mg/kg,100 mg/kg ),造模结束后大鼠以30°俯卧位放30 min后转平卧位90 min,麻醉后取材。分别测血浆中NO、CGRP,脑组织中NO、TG中pERK、TNC中CGRP和c-Fos的表达情况。探讨了Gas-D对于辣椒碱诱导的大鼠急性偏头痛模型的治疗作用及其作用机制。结果发现,辣椒碱可致疼痛相关信号蛋白 c-Fos表达增多和细胞外信号调节激酶ERK的磷酸化,Gas与Gas-D均可显著抑制上述变化,且呈现剂量相关性。此外,辣椒碱可引起血管活性物质NO、CGRP的释放增多,此效应可被Gas-D显著抑制,且具有剂量相关性。综上,Gas-D可抑制辣椒碱诱发的NO、CGRP的释放从而达到抗偏头痛作用。其作用机制可能与抑制pERK和c-Fos蛋白的表达从而抑制痛觉信号的传导有关。

关键词: 辣椒碱, 降钙素基因相关肽, c-Fos, pERK, 偏头痛

Abstract: Capsaicin can trigger certain types of pain responds by acting on C-fiber and peripheral axons in brain.The capsaicin (0.1mM) solution was injected into the cisterna magna of rats 1 h after the intragastric administration of vehicle,Gas or Gas-D (50 mg/kg,100 mg/kg).The animals were then kept in a reverse trendelenburg position (-30 degrees) for 30 min,followed by a prone position for 90 min.Then jugular vein blood of the rats was collected to detect the plasma nitro oxide (NO) and calcitonin gene related peptide (CGRP) levels;the rats were sacrificed and the whole brain were removed to determine the concentration of NO;TNC and TG were excised for immunohistochemical staining to observe the expression of CGRP,FBJ osteosarcoma oncogene protein (c-Fos) or PKR-like endoplasmic Reticulum Kinase (pERK);and they were validated by Western Blot.The results showed that Gas-D can significantly decrease the plasma NO and CGRP levels and inhibit the expression of pERK in TG and c-Fos/CGRP in TNC induced by capsaicin,and it showed a dose correlation.In conclusion,the efficacy of Gas-D on migraine is obviously effective,therefore it may be an alternate drug for the treatment of migraine.

Key words: capsaicin, CGRP, c-Fos, pERK, migraine

中图分类号: 

R285 R962