川菊止痛胶囊对偏头痛模型大鼠的改善作用及机制研究

Study on Improvement Effects and Mechanism of Chuanju Zhitong Capsule on Migraine Model Rats

目的:研究川菊止痛胶囊对偏头痛模型大鼠的改善作用及机制。方法:将SD大鼠随机分为正常组、模型组、化学药阳性对照组(佐米曲普坦片,0.004 05 g/kg)、中药阳性对照组(复方羊角颗粒,4.32 g/kg)和川菊止痛胶囊高、中、低剂量组(1.6、0.8、0.4g/kg),每组10只。每天灌胃给药1次,连续给药5 d。末次给药30 min后,除正常组外,其余各组大鼠头颈部皮下注射硝酸甘油(10 mg/kg)复制偏头痛模型。以挠头次数为指标评价造模后2 h内(30 min为一个时间段)各组大鼠行为学变化;造模4 h后,采用全自动血液流变仪检测各组大鼠全血黏度(低切、中切、高切)、血浆黏度及红细胞聚集指数、红细胞刚性指数等血液流变学参数;酶联免疫吸附试验(ELISA)检测各组大鼠血清中一氧化氮(NO)、一氧化氮合成酶(NOS)、内皮素1(ET-1)、降钙素(CGRP)和脑组织中5-羟色胺(5-HT)、5-羟基吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)水平。结果:与正常组比较,模型组大鼠在各时间段挠头次数显著增加(P<0.01);血清中NO、NOS和CGRP水平显著升高(P<0.01),ET-1水平显著降低(P<0.01);脑组织中5-HT、DA和NE水平显著降低(P<0.01),5-HIAA水平显著升高(P<0.01);全血黏度(低切)、红细胞聚集指数、红细胞刚性指数均显著升高(P<0.05),血浆黏度显著降低(P<0.01)。与模型组比较,化学药阳性对照组(0～120 min)、中药阳性对照组(60～90min)和川菊止痛胶囊高(30～120 min)、中(60～90 min)剂量组大鼠挠头次数显著降低(P<0.05或P<0.01);中药阳性对照组和川菊止痛胶囊高、中剂量组大鼠全血黏度(低切)和红细胞聚集指数显著降低(P<0.05或P<0.01);化学药阳性对照组和川菊止痛胶囊高、中剂量组大鼠血清中NO、NOS、CGRP水平显著降低(P<0.05或P<0.01),ET-1水平显著升高(P<0.01),脑组织5-HT、DA、NE水平显著升高(P<0.05或P<0.01),5-HIAA水平显著降低(P<0.05)。结论:川菊止痛胶囊对偏头痛模型大鼠的改善作用与降低血清中NO、NOS、CGRP水平及升高脑组织中5-HT、DA、NE水平有关。

OBJECTIVE:To study the improvement effect and mechanism of Chuanju zhitong capsules(CZC)on migraine model rats.METHODS:SD rats were randomly divided into normal group,model group,chemical drug positive control group(Zolmitriptan tablet,0.004 05 g/kg),TCM positive control group(Compound yangjiao capsule,4.32 g/kg),CZC high-dose,medium-dose and low-dose groups(1.6,0.8,0.4 g/kg),10 rats in each group.All rats were relevant medicine intragastrically once a day,for successive 5 days.30 min after last medication,except for normal group,rats in other groups were given glyceryl trinitrate subcutaneously(10 mg/kg)via head and neck to induce migraine model.The behavior changes of rats were evaluated using the times of scratching head as indexes within 2 h after modeling(30 min as a period of time).4 h after modeling,hemorheological parameters as whole blood viscosity(low-shearing,medium-shearing,high-shearing),plasma viscosity,erythrocyte aggregation indexes and erythrocyte rigidity indexes were determined by automatic hemorheology instrument.The levels of NO,NOS,ET-1,CGRP in serum and the levels of 5-HT,5-HIAA,DA and NE in cerebral tissue were determined by ELISA.RESULTS:Compared with normal group,the times of scratching head was increased significantly in model group at different periods(P<0.01).The serum levels of NO,NOS and CGRP were increased significantly(P<0.01),while ET-1 level was decreased significantly(P<0.01).The levels of 5-HT,DA and NE in cerebral tissue were decreased significantly(P<0.01),while 5-HIAA level was increased significantly(P<0.01).Whole blood viscosity(low-shearing),plasma viscosity,erythrocyte aggregation index and erythrocyte rigidity indexes were increased significantly(P<0.05),plasma viscosity were decreased significantly(P<0.05).Compared with model group,the times of scratching head were decreased significantly in TCM positive control group(0-120 min),TCM positive control group(60-90 min),CZC high-dose(30-120 min)and medium-dose(60-90 min)groups(P<0.05 or P<0.01).The whole blood viscosity(low-shearing)and erythrocyte aggregation indexes of TCM positive control group,CZC high-dose and medium-dose groups were decreased significantly(P<0.05 or P<0.01);the serum levels of NO,NOS and CGRP in chemical drug positive control group and CZC high-dose and medium-dose groups were decreased significantly(P<0.05 or P<0.01),while the serum level of ET-1 was increased significantly(P<0.01);the levels of 5-HT,DA and NE were increased significantly in cerebral tissue(P<0.05 or P<0.01),while the level of 5-HIAA was decreased significantly(P<0.05).CONCLUSIONS:The improvement effect of CZC on migraine model rats is associated with decreasing the serum levels of NO,NOS and CGRP and increasing the levels of 5-HT,DA and NE in cerebral tissue.