咖啡酸、阿魏酸:新的非肽类内皮素拮抗剂1

中国临床药理学与治疗学 ›› 1999, Vol. 4 ›› Issue (2): 85-92.

咖啡酸、阿魏酸:新的非肽类内皮素拮抗剂¹

王峰, 刘敏, 杨连春, 王京媛, 蔡庆, 吕敏, 李菲

中国人民解放军空军总医院, 北京 100036

收稿日期:1999-04-15 修回日期:1999-05-06 出版日期:1999-06-26 发布日期:2020-12-04
作者简介:王峰,男,副主任药师,医学硕士,目前正在主持多项国家自然科学基金研究项目,研究方向为基础药理学与临床药理学。
基金资助:
1 国家自然科学基金资助项目No.39670886

Caffeic acid, ferulic acid:a new kind of non-peptide endothel in antagonist¹

WANG Feng, LIU Min, YANG Lian-Chun, WANG Jing-Yuan, CAI Qing, LU Min, LI Fei

General Hospital of Air Force, PLA Bei jing 100036

Received:1999-04-15 Revised:1999-05-06 Online:1999-06-26 Published:2020-12-04
Supported by:
1 This supported by National Natural Scientific Foundation of China

摘要/Abstract

摘要： 目的评价桂皮酸类化合物咖啡酸和阿魏酸对内皮素(ET-1)生物效应的拮抗作用并初步探讨其拮抗ET-1 的作用机理。方法用咖啡酸与阿魏酸腹腔注射及静脉注射给药后观察其对ET-1 致小鼠急性死亡以及对大鼠升压效应、对离体主动脉条的收缩效应的拮抗作用;口服给药后考察其对醋酸去氧皮质酮(DOCA)-盐高血压大鼠ET-1 的作用, 并对DOCA-盐高血压动物模型ET-1 血浆浓度、血压和动物体重变化及心血管组织增生的影响;对ET-1、c-fos、热休克蛋白(HSP70)mRNA 基因表达的影响。结果咖啡酸和阿魏酸腹腔注射给药后能显著延长ET-1 致小鼠急性死亡时间, 与对照组相比该作用具剂量依赖性;静脉注射给药后能拮抗ET-1 引起的正常大鼠升压效应;在离体器官上可观察到咖啡酸与阿魏酸能拮抗ET-1 的缩血管效应;咖啡酸和阿魏酸长期口服给药能降低DOCA-盐高血压模型大鼠的血压、对心脏和血管的组织增生有明显的抑制作用;可降低血浆中ET-1 的浓度并可减少ET-1 引起的c-fos、HSP70 mRNA 基因表达的增加;放射性受体-配体结合实验表明, 咖啡酸和阿魏酸可竞争性地抑制ET-1 与其受体结合。结论咖啡酸和阿魏酸为新的非肽类ET-1 拮抗剂。

关键词: 内皮素, 咖啡酸, 阿魏酸, 拮抗剂

Abstract: Aim The antagonist effects of cinnamic acid compounds of caffeic acid and ferulic acid on endo thelin-1 biological responses and their antagonist mechanism to endothelin-1 were studied.Methods Caffeic acid and ferulic acid, in different dosage were separately given int raperitoneally to mice and intravenously torats.The protective effect on acute death of mouse and the vasodilatative effect on constriction of isolated rings induced by ET-1 and the change of blood pressure of normotensive rats were observed.The drugs were also administered orally to DOCA-salt hypertensive rats, and the body weight, cardio vasculartissues wet weight, gene expression of ET-1, c-fos and HSP70 mRNA, plasma levels of ET-1 in DOCA-salt hypertensive rats were measured.By binding experiment of ¹²⁵I-ET-1 with 3T3 cells.The antagonism of Caffeic acid and ferulic acid on ET-1 was determined.Results Both Caffeic acid and ferulic acid could dose-dependently delay the acute death induced by ET-1, blunt the elevation of blood pressure on normotensive rats markedly, dilate the vasoconstriction of isolated aorticrings, blunt the elevation of systolic blood pressure and development of cardiov ascular hypertrophy in DOCA-salt hypertensive rats, inhibit gene expression of ET-1, c-fos, HSP70 mRNA and decrease the plasma levels of ET-1.both of them bind compet itively with ¹²⁵I-ET-1 on 3T3 cells. Conclusion Caffeic acid and ferulic acid are a new kind non-peptide ET antagonists.

Key words: endothelin-1, Caffeic acid, ferulic acid, antagonist

中图分类号:

R969.2

王峰, 刘敏, 杨连春, 王京媛, 蔡庆, 吕敏, 李菲. 咖啡酸、阿魏酸:新的非肽类内皮素拮抗剂¹[J]. 中国临床药理学与治疗学, 1999, 4(2): 85-92.

WANG Feng, LIU Min, YANG Lian-Chun, WANG Jing-Yuan, CAI Qing, LU Min, LI Fei. Caffeic acid, ferulic acid:a new kind of non-peptide endothel in antagonist¹[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 1999, 4(2): 85-92.

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咖啡酸、阿魏酸:新的非肽类内皮素拮抗剂¹

Caffeic acid, ferulic acid:a new kind of non-peptide endothel in antagonist¹

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