Xiongzhi Dilong decoction interferes with calcitonin gene-related peptide(CGRP)-induced migraine in rats through the CGRP/iNOS pathway  

作　　者：QingWang Tao Ma Zihan Lu Meisi Liu LiweiWang Shibo Zhao Yonglie Zhao 

机构地区：[1]Department of Neurology,The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing,100029,China [2]Research Center,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing,100078,China

出　　处：《Journal of Traditional Chinese Medical Sciences》2022年第3期267-276,共10页中医科学杂志（英文）

基　　金：funded by the National Natural Science Foundation of China (81873256);the National Key R&D Program of China “Study on Modernization of Traditional Chinese Medicine”(2019YFC1709702)。

摘　　要：Objective: To evaluate the effects of Xiongzhi Dilong decoction(XZDLD) and its wind medicine on calcitonin gene-related peptide(CGRP)-induced migraine and explore the mechanism through the CGRP/inducible nitric oxide synthase(iNOS) pathway.Methods: Rats were divided into control, model, XZDLD, XZDLD(external wind), XZDLD(internal wind),and olcegepant groups. CGRP was injected into the dura mater to induce a migraine. The frequency of head scratching, cage climbing, and facial grooming was observed. The pain threshold, the levels of CGRP,pituitary adenylate cyclase activating polypeptide(PACAP), substance P(SP), and the plasma protein extravasation(PPE) ratio were measured. The phosphorylation levels of p38, extracellular signalregulated kinase 1/2(ERK1/2), and expression of iNOS were detected by western blot.Results: Compared with the model group, the three modified XZDLD groups showed reduced frequency of head scratching and cage climbing in the first 30 min(all P <.05). Facial grooming frequency was reduced in XZDLD and XZDLD(external wind) groups(P =.0003 and P =.0131, respectively). External wind medicine played a more important role in increasing mechanical pain threshold than internal wind medicine. Moreover, compared with the model group, the three modified XZDLD groups demonstrated reduced plasma levels of CGRP and PACAP(all P <.05). No difference in the SP level was observed among the six groups. XZDLD reduced PPE ratio. XZDLD and XZDLD(external wind) groups suppressed the CGRP/iNOS pathway by inhibiting the p-p38/p38 ratio and the expression of iNOS. No difference in pERK1/2/ERK1/2 ratio was detected among the six groups.Conclusion: XZDLD increases pain threshold, downregulates the expression of CGRP and PACAP, and reduces PPE ratio by inhibiting the CGRP/iNOS pathway. External wind medicine is more effective than internal one on improving facial grooming and head scratching, increasing the mechanical pain threshold, and inhibiting the expression of iNOS.

关 键 词：MIGRAINE Calcitonin gene-related peptide Plasma protein extravasation Xiongzhi Dilong decoction Wind medicine CGRP/iNOS pathway 

分 类 号：R285.5[医药卫生—中药学]