基于vWF/GPIb-IX-V信号通路的丹红注射液对急性血瘀大鼠模型活血化瘀作用及机制研究  

Effect and mechanism of Danhong Injection on promoting blood circulation and removing blood stasis in rats with acute blood stasis based on vWF/GPIb-IX-V signal pathway

作　　者：刘旭 吴宿慧[1] 陈小菲[2] 张宇航[1] 李寒冰[1] 唐进法[2] LIU Xu;WU Su-hui;CHEN Xiao-fei;ZHANG Yu-hang;LI Han-bing;TANG Jin-fa(Henan Provincial Key Laboratory of“Prevention of Disease”Health of Traditional Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Province Engineering Research Center for Clinical Application,Evaluation and Transformation of Traditional Chinese Medicine,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学河南省中医药“治未病”健康重点实验室,河南郑州450046 [2]河南中医药大学第一附属医院河南省中药临床应用、评价与转化工程研究中心,河南郑州450000

出　　处：《中草药》2023年第4期1173-1183,共11页Chinese Traditional and Herbal Drugs

基　　金：河南省中医药科学研究专项(20-21ZY1001);河南省高校科技创新团队(23IRTSTHN026)。

摘　　要：目的 观察丹红注射液对急性血瘀大鼠模型的影响,探讨丹红注射液调控血瘀证血小板功能的作用机制。方法 60只SD大鼠随机分为空白组、模型组、舒血宁注射液(1.8 mL/kg)组和丹红注射液高、中、低剂量(1.4、0.7、0.35 mL/kg)组,尾iv给予药物干预11 d后,采用sc肾上腺素联合冰水浴制备急性血瘀证大鼠模型,再给予药物干预1 d后,检测血流变指标、凝血功能指标,血小板活化黏附、聚集、释放相关指标;观察耳廓微循环、心电图和心尖、腹主动脉组织病理变化;采用qRT-PCR和Western blotting检测心肌组织蛋白激酶B1(protein kinase B1,Akt1)、p38、细胞外信号调节激酶1/2(extracellular signal-regulated kinases1/2,ERK1/2)的表达。结果 与空白组比较,模型组大鼠血液流变学、血管性血友病因子(von Willebrand factor,vWF)、纤连蛋白(fibronectin,FN)、血栓素B2(thromboxane B2,TXB2)、β-血栓环蛋白(β-thromboglobulin,β-TG)、血小板第四因子(platelet factor 4,PF4)指标显著升高(P<0.05、0.01),6-酮-前列腺素F1α(6-keto-prostaglandin F1α,6-keto-PGF1α)、耳廓微循环血流量显著降低(P<0.01),心肌组织p-Akt1、p-ERK1/2、p-p38蛋白表达以及Akt1、ERK1/2、p38基因表达水平均显著升高(P<0.01)。与模型组比较,丹红注射液能够不同程度地降低血液流变学指标、vWF、FN、TXB2、β-TG、PF4(P<0.05、0.01),升高6-keto-PGF1α(P<0.05、0.01),显著提高凝血酶时间(thrombin time,TT)值(P<0.05、0.01),保护心脏,增加耳廓微循环血流量(P<0.05)。心尖、腹主动脉组织HE染色结果显示,模型组大鼠心肌、血管内膜出现轻微损伤,弹力纤维破坏,由于斑块脱落导致开始出现空泡;丹红注射液组大鼠心肌、血管内膜和内皮细胞以及弹力纤维显著改善。结论 丹红注射液可以恢复血液流变学、凝血功能,改善血管内皮细胞、心肌细胞功能,通过调控vWF/GPIb-IX-V介导的信号通路及血小板功能,对大鼠急性血瘀Objective To observe the effect of Danhong Injection(丹红注射液)on acute blood stasis rats model,and explore the mechanism of Danhong Injection on regulating platelet function of blood stasis syndrome.Methods A total of 60 SD rats were randomly divided into blank group,model group,Shuxuening Injection(舒血宁注射液,1.8 mL/kg)group and Danhong Injection high-,medium-and low-dose(1.4,0.7,0.35 mL/kg)groups.After 11 d of drug intervention,rat model of acute blood stasis syndrome was prepared with sc adrenaline combined with ice water bath.After 1 d of drug intervention,hemorheology index,coagulation function index,platelet activation,adhesion,aggregation and release related indexes were measured;The auricle microcirculation,ECG and histopathological changes of cardiac apex and abdominal aorta were observed;The expressions of protein kinase B1(Akt1),p38 and extracellular signal-regulated kinase 1/2(ERK1/2)in myocardium was detected by qRT-PCR and Western blotting.Results Compared with blank group,hemorheology,von Willebrand factor(vWF),fibronectin(FN),thromboxane B2(TXB2),β-thrombocyclin(β-TG),platelet factor 4(PF4)were significantly increased in model group(P<0.05,0.01),6-keto-prostaglandin F1α(6-keto-PGF1α)and auricle microcirculation blood flow were significantly decreased(P<0.01),p-AKT1,p-ERK1/2 and p-p38 protein expressions and Akt1,ERK1/2,and p38 gene expressions in myocardial tissue were significantly increased(P<0.01).Compared with model group,Danhong Injection decreased the hemorheological indexes,vWF,FN,TXB2,β-TG,PF4 in different degrees(P<0.05,0.01),increased 6-keto-PGF1αand thrombin time(TT)(P<0.05,0.01),protected heart,increased auricle microcirculation blood flow(P<0.05).HE staining results of cardiac apex and abdominal aorta showed that myocardial and vascular intima of rats in model group were slightly damaged,elastic fibers were damaged,and vacuoles began to appear due to the plaque shedding;The myocardial,vascular intima,endothelial cells and elastic fibers of rats in Danhong Injectio

关 键 词：丹红注射液 急性血瘀 心血管疾病 血小板功能 血管性血友病因子 表面受体糖蛋白Ib-IX-V 

分 类 号：R285.5[医药卫生—中药学]