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一氧化氮和前列腺素在内毒素引起降钙素基因相关肽释放中的作用

王宪, 吴中欣, 唐跃明, 韩启德

(北京医科大学第三临床医院血管医学研究所，北京100083)

摘要

本实验在离体灌流大鼠肠系膜动脉床研究内毒素引起降钙素基因相关肤(CGRP)释放的机制。内毒素(50 pg/ml)使CGRP释放增加16倍，一氧化氮合成酶(NOS)底物L-精氨酸((L-
Arg)能促进内毒素引起的CGRP释放(410o), NOS抑制剂N0-硝基一L一精氨酸(L-NNA)及鸟昔
酸环化酶抑制剂甲基蓝(MB)能使内毒素的上述作用分别降低35%与3600 L一精氨酸(L-Arg )
能逆转L-NNA的作用。提示内毒素的作用机制中部分是通过一氧化氮引起细胞内cGMP升高而
介导的。用化学方法破坏血管内皮细胞，L-NNA与L-Arg的上述作用依然存在。提示内毒素主要是激活血管周围感觉神经末梢的神经源NOS，而非内皮源NOS。环氧化酶抑制剂消炎痛(Indo ）
与布洛芬(Ibu)也能使内毒素引起CGRP释放的作用分别降低34%与3900，但与L-NNA的作
用不能迭加。提示内毒素可能通过激活神经源NOS进而引起环氧化酶活化而起作用。

关键词： 降钙素基因相关肽; 内毒素; 一氧化氮; 环氧化酶

THE ROLES OF NITRIC OXIDE AND PROSTAGLANDINS IN THE ENDOTOXIN-INDUCED RELEAS RELATED PEPTIDE (CGRP) IN RAT MESENTERIC ARTERYE OF CALCITONIN GENE-

WANG XIAN, WU ZHONG-XIN, TANG YUE-MING , HAN QI-DE

(Institute of Vascular Medicine, The Third Hospital, Beijing Medical University, Beijing 100083)

Abstract

The mechanism of endotoxin (ETX)-induced release of CGRP was studied in isolated mesenteric arterial bed. ETX (50 }tg/ml) caused a 16-fold increase of the release of CGRP. The effect of ETX was enhanced by L-arginine (L-Arg)，a substratum of nitric oxide synthase (NOS)，by 41%，but inhibited by NG- nitro- L- arginine (LNNA)，an selective inhibitor of NOS，L-NNA，and methylium blue (MB)，an inhibitor of guanylate cyclase，respectively by 35%and 36%.These observations suggested that the effect of ETX is，at least partially，mediated by elevation of intracellular cGMP induced by NO. When endothelial cells were removed，the above responses of L-NNA and L-Arg still existed，indicating that ETX activated neuronal，rather than endothelial，NOS. Indomethacin and ibupofen，inhibitors of cyclooxygenase，also inhibited ETX-induced CGRP release by 34写and 39%respectively. When L-NNA and indomethacin were both incubated，no additive effects were discernible. The data suggest that ETX triggers CGRP release partially through activation of NOS located in
perivascular sensory nerve and increase of NO，which is followed by activation of c}clooxygenase.

Key words: Calcitonin gene-related peptide;Endotoxin;nitro oxide;cyclooxygenase

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引用本文：

王宪, 吴中欣, 唐跃明, 韩启德. 一氧化氮和前列腺素在内毒素引起降钙素基因相关肽释放中的作用[J]. 生理学报 1996; 48 (3): .

WANG XIAN, WU ZHONG-XIN, TANG YUE-MING , HAN QI-DE. THE ROLES OF NITRIC OXIDE AND PROSTAGLANDINS IN THE ENDOTOXIN-INDUCED RELEAS RELATED PEPTIDE (CGRP) IN RAT MESENTERIC ARTERYE OF CALCITONIN GENE- . Acta Physiol Sin 1996; 48 (3): (in Chinese with English abstract).