Inhibition of Expression of Hypoxia-inducible Factor-la mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats |
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摘 要: |
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关 键 词: | 缺氧诱导因子-1a 肺动脉高压 一氧化氮 作用因子 抵制表达 L-精氨酸 |
收稿时间: | 27 August 2003 |
Inhibition of expression of hypoxia-inducible factor-1α mRNA by nitric oxide in hypoxic pulmonary hypertension rats |
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Authors: | AO Qilin Huang Lei Zhu Pengcheng Xiong Mi Wang Dixun |
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Institution: | (1) Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan;(2) Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan |
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Abstract: | Summary In order to study the effect of nitric oxide (NO) on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) mRNA in hypoxic
pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic
hypoxic group and hypoxia plus L-argine (L-Arg) group. The animal model of HPH was developed. The mean pulmonary arterial
pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF-1α mRNA expression levels were
detected by in situ hybridization (ISH) and semiquantitative RT-PCR. It was found that after 14 days hypoxia, the mPAP in
normoxic control group (17.6±2.7 mmHg,l mmHg=0.133 kPa) was significantly lower than that in chronic hypoxic group (35.8 ±6.1
mmHg,t=0.2918,P<0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L-argine group (24.4±3.8 mmHg,t=0.2563,P<0.05). ISH showed that the expression of HIF-1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group
(0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683,t=3.125,P<0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L-argine group (0.1928±0.0381,t=2.844,P<0.05). RT-PCR showed that the content of HIF-1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times
higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L-argine group (1.4511±0.3981), respectively.
It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF-1α mRNA, which may be one of the mechanisms
through which NO affects the pathogenesis of HPH.
AO Qilin, male, born in 1971, Lecturer, M. D., Ph. D.
This project was supported by a grant from National Natural Sciences Foundation of China (No. 39730190). |
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Keywords: | nitric oxide hypoxia-inducible factor-1 alpha hypoxic pulmonary hypertension |
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