基于“病证结合”建立的肝阳上亢兼瘀血型偏头痛大鼠模型研究  

Construction of Rat Model of Migraine with Hyperactivity of Liver-Yang and Blood Stagnation Based on"Combination of Disease and Syndrome"

作　　者：朱蔷 刘顶鼎 刘冬 曾贵荣[3] 王静茹 杨菁 郭建生 吴雪梅[1] Qiang;Liu Dingding;Liu Dong;Zeng Guirong;Wang Jingru;Yang Jing;Guo Jiansheng;Wu Xuemei(Research Center for Pharmacodynamic Material Basis and Mechanism of Action,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Provincial Research Center for Safety Evaluation of Drugs,Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs,Changsha 410331,China)

机构地区：[1]贵州中医药大学药效物质基础及作用机理研究中心,贵阳550025 [2]湖南中医药大学,长沙410208 [3]湖南省药物安全评价研究中心,新药药效与安全性评价湖南省重点实验室,长沙410331

出　　处：《世界科学技术-中医药现代化》2023年第10期3264-3271,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会地区项目(82160894):芎麻汤有效部位通过调控肠道菌群介导的TRPV1-CGRP通路治疗肝阳上亢兼瘀血型偏头痛的作用及机制研究,负责人:刘顶鼎;国家自然科学基金委员会地区项目(81860844):基于TRPV1-CGRP/CGRP-R信号通路探讨芎麻汤药效部位治疗肝阳上亢兼血瘀型偏头痛机理研究,负责人:刘顶鼎;贵州中医药大学博士启动基金校级项目(贵中医博士启动[2022]07号):肝阳上亢兼瘀血型偏头痛病证结合模型研究,负责人:刘冬

摘　　要：目的利用附子汤灌胃与电刺激三叉神经节构建肝阳上亢兼瘀血型偏头痛大鼠模型,探讨该模型的特征。方法30只SD大鼠分为正常组、模型组、正天丸组(1.6 g·kg^(-1)),每组10只。模型组、正天丸组大鼠灌胃附子汤(2.00 g·kg^(-1)),每天1次,连续28天,建立肝阳上亢证;附子汤灌胃第15天,正天丸组大鼠同时给予正天丸药液,每天1次,共14天;第29天时,电刺激大鼠三叉神经节建立肝阳上亢兼瘀血型偏头痛模型。末次给药30 min后,观察大鼠宏观体征和行为表现,血液粘度仪检测血液流变学;免疫组化、RT-qPCR、Western blot法检测大鼠三叉神经颈髓复合体(TCC)中P物质(SP)阳性表达、mRNA及蛋白相对表达量。结果与正常组相比,模型组具有双目红赤,易怒,同笼打斗,舌质暗或有瘀点等宏观体征;出现有规律地摆头、频繁理毛等行为变化;中央区路程增加(P<0.05);全血高切相对粘度、血浆粘度、红细胞聚集指数均明显升高(P<0.05),红细胞变型指数明显降低(P<0.05);TCC中SP阳性表达、mRNA及蛋白相对表达量均明显升高(P<0.05)。与模型组相比,正天丸组大鼠宏观体征及行为变化明显改善;中央区路程明显减少(P<0.05);全血高切相对粘度、血浆粘度、红细胞聚集指数明显降低(P<0.05),红细胞变型指数明显升高(P<0.05);TCC中SP阳性表达、mRNA及蛋白相对表达量均明显降低(P<0.05,P<0.01)。结论SD大鼠附子汤灌胃4周结合电刺激三叉神经节可构建与临床表现基本相符的肝阳上亢兼瘀血型偏头痛模型。Objective To study the characteristics of a rat model of migraine with hyperactivity of liver-yang and blood stagnation,which was established by Fuzi Decoction combined with electrical stimulation of the trigeminal ganglion.Methods The 30 SD rats were divided into normal group,model group,and Zhengtian pill group(1.6 g·kg^(-1)),with 10 rats in each group.Rats in the model group and Zhengtian pill group were fed with aconite decoction(2.00 g·kg^(-1))once a day for 28 day to establish the hyperthermia model;On the 15 day of intragastric administration,rats in the Zhengtai pill group were simultaneously given Zhengtai pill solution once a day for 14 day;At 29 day,the trigeminal ganglion was stimulated to create the migraine model of hyperliver and stasis.After 30 min of the last dose,the macroscopic signs and behaviors were observed,and the blood rheology was detected by blood visticometer.Positive substance P(SP)expression,mRNA and relative protein expression in the trigeminal cervical pulp complex(TCC)in rat mice by immunohistochemistry,RT-qPCR and Western blot analysis.Results Compared with the normal group,the model group has macro signs such as red eyes,irritability,cage fighting,dark tongue and stasis points;regular head positioning and frequent hair management;increased distance in the central area(P<0.05).The relative viscosity of whole blood,plasma viscosity,red blood cell aggregation index all increased(P<0.05),and the red blood cell variant index decreased(P<0.05);SP positive expression,mRNA and the relative protein expression increased in TCC(P<0.05).Compared with model group,Zhengtian pill group can improve macro representation and behavior significantly;can significantly reduce central distance(P<0.05);can reduce plasma viscosity,high-shear relative viscosity of whole blood,and red blood cell aggregation index(P<0.05);increase the Red blood cell variant index significantly(P<0.05);down-regulate SP positive expression,mRNA and relative protein expression in TCC(P<0.05,P<0.01).Conclusion SD rats were u

关 键 词：偏头痛 肝阳上亢证 瘀血证 电刺激 三叉神经节 附子汤 病证结合动物模型 

分 类 号：R285.5[医药卫生—中药学]