都梁软胶囊对皮质扩布性抑制偏头痛大鼠的作用研究及机制探讨  

Study on Influence of Duliang(都梁)Soft Capsules on Migraine Rats with Cortical Spreading Depression and Its Mechanism

作　　者：韩李阳 田韦韦 华桦[2] 曾瑾[2] 刘俐 李莉[2] 王道权 黄介 鄢良春[2] 赵军宁 HAN Liyang;TIAN Weiwei;HUA Hua;ZENG Jin;LIU Li;LI Li;WANG Daoquan;HUANG Jie;YAN Lianghun;ZHAO Juning(College of Pharmacy,Sichuan University,Chengdu610041;Sichuan Academy of Chinese Medicine Sciences,Sichuan Institute for Translational Chinese Medicine,Biological Assay Key Laboratory of National Administration of Traditional Chinese Medicine for Traditional Chinese Medicine Quality,Translational Chinese Medicine Key Laboratory of Sichuan Province,Sichuan Engineering Technology Research Center of Genuine Regional Drug,Engineering Research Center for Formation Principle and Quality Evaluation of Genuine Medicinal Materials in Sichuan Province,Laboratory for Rapid Detection of Toxicity of Traditional Chinese Medicine in Sichuan Provincial Administration of Chinese Medicine,Chengdu 610041;Chongqing Pharscin Pharmaceutical Group Co.,Ltd.,Chongqing 401121)

机构地区：[1]四川大学药学院,成都610041 [2]四川省中医药科学院,四川省中医药转化医学中心,国家中医药管理局中药质量生物评价重点研究室,中医药转化医学四川省重点实验室,四川省道地药材系统开发工程技术研究中心,四川省道地药材形成原理与品质评价工程研究中心,四川省中医药管理局中药毒性快速检测实验室,成都610041 [3]重庆华森制药有限公司,重庆401121

出　　处：《中药药理与临床》2023年第7期27-33,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省中医药管理局科学技术研究专项课题(编号:2021ZD001);四川省科技厅基本科研业务专项(编号:A-2021N-Z-4);四川省科技计划重点研发项目(编号:2020YFS0566)。

摘　　要：目的:应用氯化钾刺激建立皮质扩布性抑制(Cortical spreading depression,CSD)偏头痛大鼠模型,研究都梁软胶囊对CSD大鼠的改善作用及机制。方法:按照体质量将大鼠随机分层分为正常对照组、模型对照组、氟桂利嗪2.7 mg/kg组和都梁软胶囊0.32、0.65、1.30 g(内容物)/kg组,每组15只,各组灌胃相应药物或同体积溶媒,1次/d,连续给药7 d。末次给药30 min后以浸有定量3 mol/L氯化钾溶液的滤纸片于大鼠硬脑膜表面刺激大鼠枕叶皮质,复制CSD偏头痛大鼠模型。记录刺激前后CSD大鼠的大脑额叶皮质的脑电信号;采用ELISA法测定CSD大鼠血浆及脑干中降钙素基因相关肽(Calcitonin-generelated peptide,CGRP)和P物质(Substance P,SP)的含量;用免疫组织化学法(IHC)检测CSD大鼠氯化钾刺激侧皮质原癌基因(C-FOS)的表达。结果:与正常对照组比较,模型对照组大鼠氯化钾刺激1 h内皮质脑电信号的波幅标准化值显著降低,血浆和脑干CGRP含量显著升高(P<0.01),脑干SP含量明显升高,刺激侧皮质C-FOS的表达显著升高(P<0.05);与模型对照组比较,都梁软胶囊0.32、0.65 g/kg组大鼠氯化钾刺激1 h内皮质脑电信号的波幅标准化值明显升高,0.32 g/kg组脑干组织CGRP、SP含量,0.65 g/kg组血浆CGRP、脑干SP含量以及1.30 g/kg组血浆和脑干CGRP含量明显降低,0.65、1.30 g/kg组刺激侧皮质C-FOS的蛋白表达明显降低(P<0.05或P<0.01)。结论:都梁软胶囊预防给药对CSD大鼠具有一定的对抗作用,其可以改善CSD大鼠皮质脑电的抑制状态,降低刺激侧皮质C-FOS高表达,下调中枢及外周血管活性神经肽CGRP以及SP的表达。Objective:The model of migraine rats with cortical spreading depression(CSD)was established by potassium chloride stimulation,and the improvement effect and mechanism of Duliang(都梁)soft capsules on rats with CSD were studied.Methods:According to the body weight,rats were randomly divided into the normal control group,model control group,group with flunarizine of 2.7 mg/kg,and groups with Duliang soft capsules(content)of 0.32,0.65,and 1.30 g/kg,with 15 rats in each group.Each group was given intragastric administration of corresponding drugs or solvents with the same volume once a day,for consecutive seven days.30 minutes after the last administration,the model of migraine rats with CSD was established by placing filter paper with potassium chloride solution of 3 mol/L on the dura mater surface of the rats to stimulate their occipital cortexes.The electrocorticography(EEG)signals of the frontal cortexes of the rats with CSD were recorded before and after the stimulation.The expressions of the C-FOS in the lateral cortexes of the rats with CSD stimulated by potassium chloride were detected by immunohistochemistry(IHC).The expression levels of calcitonin-gene-related peptide(CGRP)and substance P(SP)in the brainstem and plasma of rats with CSD were detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with that in the normal control group,the normalized amplitude of cortical EEG signals of the rates in the model control group stimulated by potassium chloride within 1 h reduced,and the expression level of C-FOS in the stimulated lateral cortex increased.The CGRP of plasma and brainstem was up-regulated significantly(P<0.01),and the SP of the brainstem was up-regulated(P<0.05).Compared with that in the model control group,the normalized amplitude of cortical EEG signals of the rates in groups with Duliang soft capsules(content)of 0.32 and 0.65g/kg stimulated by potassium chloride within 1 h increased,while the expression level of C-FOS in stimulated lateral cortex of the rats in groups with Duliang

关 键 词：都梁软胶囊 皮质扩布性抑制 偏头痛 降钙素基因相关肽 P物质 

分 类 号：R285.5[医药卫生—中药学]