丹灯通脑胶囊抗血栓作用及其作用机制的研究
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摘要
目的研究丹灯通脑胶囊抗血栓作用及其作用机制。方法 D大鼠随机分为空白组、模型组、阿司匹林9mg·kg~(-1)组和丹灯通脑胶囊378、126、42mg·kg~(-1)组,灌胃给药1日1次,连续给药6d,空白组和模型组给予等体积蒸馏水。采用肾上腺素加冰浴的方法复制血瘀大鼠模型,观察丹灯通脑胶囊对血瘀大鼠血液流变学、ADP诱导的血小板聚集、纤溶凝血系统功能(PT,TT,APTT和FIB)、血浆血栓烷B2,前列环素水平及纤溶酶原激活物抑制因子的活性影响,来探讨丹灯通脑胶囊的抗血栓作用机理。结果与模型组比较,丹灯通脑胶囊各剂量组全血低、中、高切黏度均显著降低(P<0.01或P<0.05),378mg·kg~(-1)剂量组红细胞聚集指数显著降低(P<0.01);各剂量组ADP诱导的血小板聚集率显著降低(P<0.01或P<0.05),血浆APTT显著增加(P<0.01或P<0.05);各剂量组TXB2值显著降低(P<0.01),378、126mg·kg~(-1)组6-KetoPGF1a值和6-Keto-PGF1a/TXB2升高(P<0.05),378mg·kg~(-1)组PAI值降低(P<0.05),各项指标均呈现剂量相关性。结论丹灯通脑胶囊具有明显的抗血栓作用。其抗血栓作用机制可能与抑制血栓烷A2合成,促进前列环素的合成,降低血浆纤溶酶原激活物抑制因子的活性有关。
OBJECTIVE To explore the antithrombotic effect and its molecular mechanism of Dandengtongnao capsules(DTNC).METHODS SD rats were randomly divided into bland group,model group,aspirins 9mg·kg~(-1)group and DTNC 378,126,42mg·kg~(-1)three dosages groups,oral administration once a day,total 6 days.The blank group and model group were given the same volume distilled water.The model of rat blood stasis,Which was induced with subcutaneous injection of adrenaline of adrenaline hydrochloride and being socked in ice-water,was experimented to observe effect of DTNC on bloodrheology,ADP-induced platelet aggregation,coagulation and fibrinolysis system(PT,TT,APTT,FIB),the plasma levels of TXB2,6-Keto-PGF1 a and PAI activity.RESULTS Compared with the model group,Every-dosage group of DTNC could decreased the whole blood viscosity(P<0.01 or P<0.05) and the378mg·kg~(-1)dosage group could also reduced the erythrocyte aggregation(P<0.01);Every-dosage group? of DTNC significantly reduced ADP-induced platelet aggregation rate(P<0.01 or P<0.05) and TXB2values(P<0.01),and markedly increased APTT values(P<0.01 or P<0.05),which positively relates to the dosage.378mg·kg~(-1)dosage group of DTNC could increased the 6-Keto-PGF1 a values and 6-Keto-PGF1a/TXB2,decreased PAI values(P<0.05).CONCLUSION There was apparently antithrombotic effect of DTNC.The mechanism may be related with inhibits TXA2 synthesis,promote prostacyclin synthesis,and lowers PAI-1 activity.
OBJECTIVE To explore the antithrombotic effect and its molecular mechanism of Dandengtongnao capsules(DTNC).METHODS SD rats were randomly divided into bland group,model group,aspirins 9mg·kg~(-1)group and DTNC 378,126,42mg·kg~(-1)three dosages groups,oral administration once a day,total 6 days.The blank group and model group were given the same volume distilled water.The model of rat blood stasis,Which was induced with subcutaneous injection of adrenaline of adrenaline hydrochloride and being socked in ice-water,was experimented to observe effect of DTNC on bloodrheology,ADP-induced platelet aggregation,coagulation and fibrinolysis system(PT,TT,APTT,FIB),the plasma levels of TXB2,6-Keto-PGF1 a and PAI activity.RESULTS Compared with the model group,Every-dosage group of DTNC could decreased the whole blood viscosity(P<0.01 or P<0.05) and the378mg·kg~(-1)dosage group could also reduced the erythrocyte aggregation(P<0.01);Every-dosage group? of DTNC significantly reduced ADP-induced platelet aggregation rate(P<0.01 or P<0.05) and TXB2values(P<0.01),and markedly increased APTT values(P<0.01 or P<0.05),which positively relates to the dosage.378mg·kg~(-1)dosage group of DTNC could increased the 6-Keto-PGF1 a values and 6-Keto-PGF1a/TXB2,decreased PAI values(P<0.05).CONCLUSION There was apparently antithrombotic effect of DTNC.The mechanism may be related with inhibits TXA2 synthesis,promote prostacyclin synthesis,and lowers PAI-1 activity.
引文
[1]张时东.丹灯通脑软胶囊治疗急性脑梗死的疗效观察[J].首都医药,2014,(8):47-48.
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[9]池响峰,聂斌,张曼玲,等.丹灯通脑软胶囊配合扶阳灸改善脑卒中患者后循环缺血45例临床观察[J].中医药导报,2014,20(12):63-65.
[10]李仪奎.中药药理实验方法学(第二版)[M].上海:上海科技出版社,2006,144-146.
[11]和岚,蒋文跃,毛腾敏.注射肾上腺素模拟“气滞”复制急、慢性血瘀模型初探[J].中国中西医结合杂志,2004,24(3):244-246.
[12]赵建宏,林琳,高继发,等.SD大鼠血管内皮细胞损伤模型的制作方法[J].微循环学杂志,2000,10(2):20-21.
[13]袁淑娟,张志伟,高天红,等.红花注射液抗血栓作用机制研究[J].中国中药杂志,2011,36(11):1528-1529.
[14]韩淑燕,李海霞,文宗曜,等.三七总皂苷对急性血瘀大鼠血液流变学的改善作用[J].中国药理学与毒理学杂志,2009,23(3):183-187.
[15]王硕,张晓天,胡亚,等.血栓心脉宁片对急性血瘀大鼠血浆TXA2及PGI2含量的影响[J].中西医结合心脑血管病杂志,2012,10(6):712-713.
[2]魏文化,白莉,司霞.丹灯通脑胶囊治疗脑梗死后遗症临床观察[J].河南实用神经疾病杂志,2012,15(5):51-52.
[3]张敬华,黄迟,张臻年,等.丹灯通脑胶囊治疗脑梗死恢复期30例临床观察[J].中医药导报,2014,20(7):109-110.
[4]刘宇明,许治强,匡永锋.丹灯通脑软胶囊治疗脑梗死恢复期临床疗效观察[J].中华全科医学,2012,10(4):530,602-602.
[5]沈维青,刘柏林,邹颖.丹灯通脑软胶囊辅助康复训练辨治脑梗死恢复期的临床研究[J].时珍国医国药,2015,26(3):652-653.
[6]马淑义.丹灯通脑软胶囊辅助康复训练治疗脑梗死恢复期的疗效评价[J].中国实用神经疾病杂志,2016,19(19):98-99.
[7]李辰佳.丹灯通脑软胶囊治疗椎-基底动脉供血不足性眩晕47例[J].山东中医杂志,2009,28(6):392-393.
[8]郑萍红,李飞泽,陈琳.丹灯通脑胶囊联合银杏达莫注射液治疗后循环缺血性眩晕42例[J].浙江中医杂志,2013,48(3):229-230.
[9]池响峰,聂斌,张曼玲,等.丹灯通脑软胶囊配合扶阳灸改善脑卒中患者后循环缺血45例临床观察[J].中医药导报,2014,20(12):63-65.
[10]李仪奎.中药药理实验方法学(第二版)[M].上海:上海科技出版社,2006,144-146.
[11]和岚,蒋文跃,毛腾敏.注射肾上腺素模拟“气滞”复制急、慢性血瘀模型初探[J].中国中西医结合杂志,2004,24(3):244-246.
[12]赵建宏,林琳,高继发,等.SD大鼠血管内皮细胞损伤模型的制作方法[J].微循环学杂志,2000,10(2):20-21.
[13]袁淑娟,张志伟,高天红,等.红花注射液抗血栓作用机制研究[J].中国中药杂志,2011,36(11):1528-1529.
[14]韩淑燕,李海霞,文宗曜,等.三七总皂苷对急性血瘀大鼠血液流变学的改善作用[J].中国药理学与毒理学杂志,2009,23(3):183-187.
[15]王硕,张晓天,胡亚,等.血栓心脉宁片对急性血瘀大鼠血浆TXA2及PGI2含量的影响[J].中西医结合心脑血管病杂志,2012,10(6):712-713.