【作者】 侯敏； 陈烈春； 李燕君； 薛强； 刘杨； 杨盛； 童杰； 徐晓玉；

【Author】 Min Hou;Liechun Chen;Yanjun Li;Qiang Xue;Yang Liu;Sheng Yang;Jie Tong;Xiaoyu Xu;Pharmacological Evaluation Engineering Research Center of Chongqing,Institute of Chinese Medicine of Southwest University;Hua Sen Pharmaceutical Products Ltd.;

【机构】 第三军医大学大坪院药剂科； 西南大学药学院； 西南大学中药研究所,国家中医药管理局； 重庆华森制药有限公司；

【摘要】 偏头痛是一种严重影响人们生活质量的疾病,都梁软胶囊是由重庆华森制药有限公司生产的上市中成药（国药准字:Z20055185）,由川芎和白芷两味中药组成,在临床上常用于治疗头痛属风寒瘀血阻滞脉络证者,但对于偏头痛的治疗一直缺乏相关的药效学试验依据,其作用机制也不得而知。目的:研究都梁软胶囊对偏头痛模型大鼠的治疗效果及其作用机制。方法:采用硝酸甘油致大鼠偏头痛模型,观察都梁软胶囊对偏头痛模型大鼠行为学的影响,以评价其药效:再观察对偏头痛模型大鼠血浆CGRP、ET、血清NO和脑干单胺类递质5-HT、NE、DA及脑干胞核蛋白NF-κB P65、c-fos及总蛋白iNOS、IL-1β、COX-2的影响,以探索其作用机制。结果:药效方面,与模型组相比,都梁软胶囊1.31g·kg^-1、3.93g·kg^-1组大鼠挠头和爬笼次数显著减低（P<0.05或P<0.01）,爬笼和耳红消失的时间显著缩短（P<0.01）。作用机制方面,都梁软胶囊3.93 g·kg^-1组大鼠血浆ET含量显著升高（P<0.01）,1.31 g·kg^-1、3.93 g·kg^-1组大鼠血浆CGRP、血清NO含量、脑干单胺类递质5-HT、NE、DA及脑干炎症相关因子胞核蛋白NF-κB P65、c-fos和总蛋白iNOS、IL-1β、COX-2的表达水平显著降低（P<0.05或P<0.01）。结论:都梁软胶囊治疗偏头痛的效果明显,且其作用机制可能与调节血管活性物质、脑内单胺类递质及脑内炎症相关因子表达的异常变化有关。更多还原

【Abstract】 Migraine was a disease that seriously affected individual life.Du Liang soft capsule（DL）,a Chinese patent medicine（CPM） approved by the State Food and Drug Administration（SFDA） of China（National medical License Number:Z20055185） and produced by Chongqing Pharscin pharmaceutical Co.,LTD,was one of TCM recipes for treatment of headache resulted from cold-wind,which was composed of the two Chinese herbal drugs Rhizome Ligustici（Chuanxiong） and Radix Angelicae dahuricae（Baizhi）.However,it was always short of related pharmacodynamics experiment basis for treating migraine,and its mechanism was also unknown.In the present study,we sought to elucidate pharmacodynamic action and its mechanism of DL in an animal model of migraine induced by nitroglycerin.In the pharmacodynamic action assay,DL could greatly improve behavior changes of migraine rats,including the symptom of the scratching head,climbing cage,and appearing red ear.DL(1.31,3.93 g·kg^-1) could significantly reduce the numbers of scratching head and climbing cage of GTN-induced migraine rats（P<0.05 or P<0.01）,and markedly shorten the total time of climbing cage and red ear symptom（P<0.01）.In the mechanism assay,compared with the control group,the levels of plasma calcitonin gene related to peptide（CGRP）,serum nitric oxide（NO） and contents of brainstem 5-hydroxytryptamine（5-HT）,norepinephrine（NE） and dopamine（DA） in DL(1.31,3.93 g·kg^-1) administration groups were significantly decreased（P<0.05 or P<0.01）,and the levels of plasma endothelin（ET） was remarkably increased in DL(3.93 g·kg^-1) administration group（P<0.01）.Moreover,down-regulation of nuclear factor kappa B p65（NF-κB P65）,nuclear c-fos and pro-inflammatory cytokines including inducible nitric oxide synthase（iNOS）,Interleukin（IL）-1β,cyclooxygenase-2（COX-2） in the brainstem in DL(1.31,3.93 g·kg^-1)administration groups were determined by western blotting.The above results suggested DL has an effective therapeutical action on migraine,and its mechanism may be related to adjusting the abnormal level of neurotransmitters and vasoactive substances,consequently relieving neurogenic inflammation.更多还原