艾叶提取物对凝血因子Ⅻ的作用机制和药效物质研究  

Study on coagulation factorⅫaction mechanism under extract of Artemisia argyi and its pharmacodynamic substances

作　　者：王珊珊[1] 徐昊[1] 陈青[2] 谭开云 凌云 葛金文[1,3] WANG Shan-shan;XU Hao;CHEN Qing;TAN Kai-yun;LING Yun;GE Jin-wen(Hunan Province Key Lab of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;Medical Dept, the First Hospital of Hunan University of Chinese Medicine, Changsha 410008, China;College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China)

机构地区：[1]湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室,湖南长沙410208 [2]湖南中医药大学第一附属医院医务科,湖南长沙410008 [3]湖南中医药大学中西医结合学院,湖南长沙410208

出　　处：《中国药理学通报》2020年第8期1152-1157,共6页Chinese Pharmacological Bulletin

基　　金：湖南省高等学校“国内一流培育学科”中西医结合学科经费;湖南省教育厅一般项目(No 18C0357);湖南中医药大学创新创业训练计划项目(No X201910541050)。

摘　　要：目的观察艾叶提取物对FⅫ的作用位点并检测其所含物质,阐明其抗凝、促凝机制及药效物质基础。方法检测艾叶提取物干预下脑缺血病人血浆凝血4项、FⅫ活性;FⅫ、FⅫ-2含量;检测艾叶LODB1-6干预下血浆凝血3项、连续血浆凝固时间、FⅫ激活。液质联用分析LODB5。结果艾叶提取物延长了血浆APTT、PT、TT,降低高岭土对FⅫ的激活作用;各剂量组降低了FⅫ含量,但只有中、高剂量组FⅫ-2的含量降低。相比于LODB1-3,LODB5、6可延长APTT,LODB5还使TT延长;LODB5高剂量组和LODB6各剂量组FⅫ含量降低。液质联用分析LODB5,得到6种含量较高物质。结论艾叶提取物激活FⅫ产生促凝活性与EGF-Like2结构域有关。但艾叶提取物对脑缺血病人血浆整体表现出抗凝活性。其药效物质基础可能是异戊酸冰片酯、紫花牡荆素、棕矢车菊素、伞形花内酯、5,6,4′-三羟基-7,3′-二甲氧基黄酮、丁香酚。Aim To observe the action site of FⅫunder extract of Artemisia argyi and to detect the substances in it,so as to clarify the anticoagulant mechanism of the extract of Artemisia argyi and the substance basis of its efficacy.Methods The four items of blood coagulation and FⅫactivity in plasma were detected under the intervention of Artemisia argyi extract.The activation of FⅫand FⅫ-2 by Artemisia argyi extract was detected;the effects of LODB1-6 on three items of blood coagulation of plasma were detected,and the effects of different components on blood coagulation time were continuously monitored;the activation of FⅫby LODB1-6 was detected.LODB5 was analysed by LC-MS.Results The Artemisia argyi extract prolonged APTT,PT,TT of patients’plasma and reduced the activation effect of kaolin on FⅫ;the content of FⅫin all groups decreased,but the content of FⅫ-2 in middle and high groups decreased.Compared with LODB1-3,APTT of LODB5 and 6 were prolonged,and TT of LODB5 was prolonged.Compared with LODB1-3,the content of FⅫin high dose group of LODB5 and all groups of LODB6 were lower than that of control group.With analysis of LODB5 by LC-MS,six higher content substances were obtained.Conclusions The Artemisia argyi extract can activate FⅫto produce procoagulant activity,which is related to EGF-Like2 domain.However,it has anticoagulant activity in plasma of patients with cerebral ischemia.Its pharmacodynamic basis may be borneol isovalerate,corncobolin,5,6,4′-trihydroxy-7,3′-dimethoxyflavone,umbellifera lactone,eugenol,vitexin.

关 键 词：凝血因子Ⅻ 艾叶提取物 EGF-Like2结构域 脑缺血 血液凝固 抗凝血 

分 类 号：R282.71[医药卫生—中药学] R284.1[医药卫生—中医学]