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丝裂素活化蛋白激酶参与内皮素刺激的兔主动脉平滑肌细胞增生

李田昌, 咚利家, 庞水正, 刘秀华, 王雪清, 胡大一, 唐朝枢

，北京红十字朝阳医院心脏中心，北京100020

摘要

内皮素(endothelin, ET)是已知的体内活性最强的缩血管物质，其缩血管作用由G蛋白偶联受体所介导。但ET强大的促血管平滑肌细胞(VSMC)增生效应的机理尚未完全阐明。本研究选用培养的兔胸主动脉VSMC，探讨丝裂素活化蛋白激酶(MAPK)在ET促细胞增生中的作
用。结果表明:ET-1呈时间和浓度依赖性地促进细胞摄取“H-TdR和激活MAPK，此作用可被蛋白激酶C (protein kinase C, PKC)抑制剂Staurosporine (STP), H-7和ET、受体拮抗剂BQ123所抑制，但不被酪氨酸激酶抑制剂Herbimycin A (Herb)所抑制，用PKC激动剂PMA (phorbol myristate acetate、预处理VSMC，使其PKC活性下调，可显著减弱ET-1对MAPK的激活能力。结果提示:(l) MAPK参与ET-1所致的VSMC增生;(2) ET-促细胞增生与激活MAPK的作用是由ET、受体和PKC介导的。

关键词： 丝裂素活化蛋白激酶; 内皮素; 蛋白激酶C; 血管平滑肌细胞

ENDOTHELIN-STIMULATED PROLIFERATION OF THORACIC ARTERY SMOOTH MUSCLE CELLS INVOLVES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE

LI TIAN-CHANG，TONG LI-JIA, PANG YONG-ZHENG, LIU XIU-HUA, WANG XUE-QING, HU DA-YI, TANG CHAD-SHU

(Heart Center of Beijing Red Cross Chaoyang Hospital, Beijing 100020； Beijing Medical University, Institute of Cardiovascular Research, Beijing 100083)

Abstract

Endothelin (ET) is a potent vasoconstrictor whose responses are mediated through a common G-protein coupled receptor. So far little is known concerning its potential mitogenic capacity. In the present study，experiments were conducted to determine the role of mitogen-activated protein kinase (MAPK)activation in the rabbit thoracic artery smooth muscle cells (VSMC)in response to stimulation by ET-1 .It was found that ET-1 produced concentration- and time-dependent increases in 3H-TdR incorporation and in MAPK activity of these cells. All the increases were inhibited by protein kinase C (PKC) inhibitors，such as Staurosporine (STP) and H-7 and by ETA receptor antagonist BQ 12 3，but not by specific tyrosine kinase inhibitor Herbimycin A (Herb).Pre-
treatment with PKC activator PMA (phorbol myristate acetate) for 24 h (PKC downreg ulation)significantly attenuated ET-1一induced MAPK activation. These results indicate that:(1)ET- l-stimulated proliferation of VSMC involves the activation of MAPK and (2)ET-1-induced MAPK activation is mediated through ETA receptor and PKC.

Key words: Mitogen-activated protein kinase;Endothelin;;

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引用本文：

李田昌, 咚利家, 庞水正, 刘秀华, 王雪清, 胡大一, 唐朝枢. 丝裂素活化蛋白激酶参与内皮素刺激的兔主动脉平滑肌细胞增生[J]. 生理学报 1996; 48 (4): .

LI TIAN-CHANG，TONG LI-JIA, PANG YONG-ZHENG, LIU XIU-HUA, WANG XUE-QING, HU DA-YI, TANG CHAD-SHU. ENDOTHELIN-STIMULATED PROLIFERATION OF THORACIC ARTERY SMOOTH MUSCLE CELLS INVOLVES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE. Acta Physiol Sin 1996; 48 (4): (in Chinese with English abstract).