川菊止痛胶囊对偏头痛模型大鼠的改善作用及机制研究
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摘要
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 mediumdose 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.
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 mediumdose 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.
引文
[1]刘建林,彭成,潘媛,等.元胡止痛胶囊对偏头痛大鼠的影响[J].中药药理与临床,2013,29(4):11-13.
[2]ONG JJY,DE FELICE M.Migraine treatment:current acute medications and their potential mechanisms of action[J].Neurotherapeutics,2018,15(2):274-290.
[3]林燕,张文,武陈涛.偏头痛患者脑血管病一级预防证据评价[J].中国现代神经疾病杂志,2015,15(1):33-38.
[4]ROSHNI R.Neurogenic inflammation and its role in migraine[J].Semin Immunopathol,2018,3(40):301-314.
[5]周仲英.中医内科学[M].北京:中国中医药出版社,2004:303-309.
[6]尚艳杰,王顺.川菊止痛胶囊治疗血瘀型偏头痛50例疗效观察[J].中国中医药科技,2004,11(5):311-312.
[7]王顺,蔡玉颖,周振坤,等.川菊止痛胶囊对偏头痛患者血浆内皮素水平的影响[J].中国中医药科技,2002,9(4):203-204.
[8]张慧,李冬霞,栗志勇,等.川芎石膏汤对硝酸甘油致偏头痛大鼠血浆NO、NOS、CGRP及脑中5-HT、5-HIAA含量的影响[J].中国实验方剂学杂志,2014,20(17):175-180.
[9]SUN YY,ZHANG WJ,DONG CL,et al.Baicalin alleviates nitroglycerin-induced migraine in rats via the trigeminovascular system[J].Phytother Res,2017,31(6):899-905.
[10]李世东,吴文波,尹慧荣,等.益气化瘀颗粒对小鼠胃肠动力和大鼠血液流变学的影响[J].中国药房,2017,28(4):515-518.
[11]HOU M,TANG Q,XUE Q,et al.Pharmacodynamic action and mechanism of du liang soft capsule,a traditional Chinese medicine capsule,on treating nitroglycerin-induced migraine[J].J Ethnopharmacol,2017.DOI:10.1016/j.jep.2016.11.025.
[12]张艳.复方羊角颗粒治疗偏头痛43例[J].河南中医,2017,37(4):630-632.
[13]刘伟,来华安.复方羊角胶囊治疗头痛100例临床疗效观察[J].陕西中医学院学报,2002,25(4):21-23.
[14]袁华.复方羊角颗粒联合氟桂利嗪治疗偏头痛的疗效观察[J].中医临床研究,2014,6(9):16-21.
[15]张馨,王野成.佐米曲普坦治疗无先兆性偏头痛临床疗效研究[J].北华大学学报,2014,15(3):355-357.
[16]赵岩.头痛汤对偏头痛大鼠模型中脑导水管周围灰质cfos、c-jun基因表达影响[D].济南:山东中医药大学,2006.
[17]姜维,韦华梅,赵美,等.大鼠偏头痛模型的制作改进及评判指标选择[J].现代生物医学进展,2015,15(9):1623-1627.
[18]董兰真,蒲圣雄.偏头痛与神经源性炎症的研究进展[J].重庆医学,2015,44(8):1126-1128.
[19]MALHOTRA R.Understanding migraine:potential role of neurogenic inflammation[J].Ann Indian Acad Neurol,2016,19(2):175-182.
[20]YAKSH TL,ALLEN JW,VEESART SL,et al.Role of meningeal mast cells in trathecal morphine-evoked granuloma formation[J].Anesthesiology,2013,118(3):664-678.
[21]倪红霞,王春梅.白芷总香豆素联合白芷挥发油对大鼠偏头痛的预防作用及机制[J].吉林大学学报,2018,44(3):487-492.
[22]DRUMMOND PD.Effect of trytophan depletion on symptoms of motion sickness in migraineurs[J].Neurology,2005,65(4):620-622.
[23]刘洁,李利民,宁楠,等.半夏泻心汤对偏头痛模型大鼠血液流变学及神经递质影响的实验研究[J].成都中医药大学学报,2015,38(1):13-20.
[2]ONG JJY,DE FELICE M.Migraine treatment:current acute medications and their potential mechanisms of action[J].Neurotherapeutics,2018,15(2):274-290.
[3]林燕,张文,武陈涛.偏头痛患者脑血管病一级预防证据评价[J].中国现代神经疾病杂志,2015,15(1):33-38.
[4]ROSHNI R.Neurogenic inflammation and its role in migraine[J].Semin Immunopathol,2018,3(40):301-314.
[5]周仲英.中医内科学[M].北京:中国中医药出版社,2004:303-309.
[6]尚艳杰,王顺.川菊止痛胶囊治疗血瘀型偏头痛50例疗效观察[J].中国中医药科技,2004,11(5):311-312.
[7]王顺,蔡玉颖,周振坤,等.川菊止痛胶囊对偏头痛患者血浆内皮素水平的影响[J].中国中医药科技,2002,9(4):203-204.
[8]张慧,李冬霞,栗志勇,等.川芎石膏汤对硝酸甘油致偏头痛大鼠血浆NO、NOS、CGRP及脑中5-HT、5-HIAA含量的影响[J].中国实验方剂学杂志,2014,20(17):175-180.
[9]SUN YY,ZHANG WJ,DONG CL,et al.Baicalin alleviates nitroglycerin-induced migraine in rats via the trigeminovascular system[J].Phytother Res,2017,31(6):899-905.
[10]李世东,吴文波,尹慧荣,等.益气化瘀颗粒对小鼠胃肠动力和大鼠血液流变学的影响[J].中国药房,2017,28(4):515-518.
[11]HOU M,TANG Q,XUE Q,et al.Pharmacodynamic action and mechanism of du liang soft capsule,a traditional Chinese medicine capsule,on treating nitroglycerin-induced migraine[J].J Ethnopharmacol,2017.DOI:10.1016/j.jep.2016.11.025.
[12]张艳.复方羊角颗粒治疗偏头痛43例[J].河南中医,2017,37(4):630-632.
[13]刘伟,来华安.复方羊角胶囊治疗头痛100例临床疗效观察[J].陕西中医学院学报,2002,25(4):21-23.
[14]袁华.复方羊角颗粒联合氟桂利嗪治疗偏头痛的疗效观察[J].中医临床研究,2014,6(9):16-21.
[15]张馨,王野成.佐米曲普坦治疗无先兆性偏头痛临床疗效研究[J].北华大学学报,2014,15(3):355-357.
[16]赵岩.头痛汤对偏头痛大鼠模型中脑导水管周围灰质cfos、c-jun基因表达影响[D].济南:山东中医药大学,2006.
[17]姜维,韦华梅,赵美,等.大鼠偏头痛模型的制作改进及评判指标选择[J].现代生物医学进展,2015,15(9):1623-1627.
[18]董兰真,蒲圣雄.偏头痛与神经源性炎症的研究进展[J].重庆医学,2015,44(8):1126-1128.
[19]MALHOTRA R.Understanding migraine:potential role of neurogenic inflammation[J].Ann Indian Acad Neurol,2016,19(2):175-182.
[20]YAKSH TL,ALLEN JW,VEESART SL,et al.Role of meningeal mast cells in trathecal morphine-evoked granuloma formation[J].Anesthesiology,2013,118(3):664-678.
[21]倪红霞,王春梅.白芷总香豆素联合白芷挥发油对大鼠偏头痛的预防作用及机制[J].吉林大学学报,2018,44(3):487-492.
[22]DRUMMOND PD.Effect of trytophan depletion on symptoms of motion sickness in migraineurs[J].Neurology,2005,65(4):620-622.
[23]刘洁,李利民,宁楠,等.半夏泻心汤对偏头痛模型大鼠血液流变学及神经递质影响的实验研究[J].成都中医药大学学报,2015,38(1):13-20.