新化合物哌芳安他抗大鼠和兔动脉粥样硬化作用机理的初步研究

新化合物哌芳安他抗大鼠和兔动脉粥样硬化作用机理的初步研究

山丽梅, 张锦超, 赵艳玲, 汪海^*

1.解放军第302医院药学部, 北京 100039;
2.军事医学科学院生物工程研究所, 北京 100071;
3.军事医学科学院毒物药物研究所, 北京 100850

收稿日期:2003-10-18 修回日期:2004-02-10 出版日期:2004-03-15 发布日期:2004-03-15
通讯作者: 汪海*

Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis

SHAN Li-mei, ZHANG Jin-chao, ZHAO Yan-ling, WANG Hai^*

1.Department of Pharmacy, 302nd Hospital of PLA, Beijing 100039;
2.Institute o f Biotechnology, Beijing 100071;
3.Institute of Pharmacology and Toxicology, Beijing 100850, China

Received:2003-10-18 Revised:2004-02-10 Online:2004-03-15 Published:2004-03-15
Contact: WANG Hai*

摘要/Abstract

摘要： 目的在早期和晚期动脉粥样硬化模型上研究新化合物哌芳安他抗动脉粥样硬化的机制. 方法大鼠或家兔随机分为正常对照、模型对照和哌芳安他给药组, 其中模型对照和哌芳安他给药组动物给予高胆固醇饲料, 检测的指标包括: 兔颈动脉HE染色; 大鼠或兔血清TC, LDL-CHO, HDL-CHO, IL-8, ET-1, PGI2, TXA2 和NO水平; 兔颈动脉MCP-1和 IL-8 mRNA表达量. 结果哌芳安他能明显抑制早期和晚期动脉粥样硬化中TXA2的过量表达, 在大鼠早期动脉粥样硬化中可见哌芳安他给药组动物血清NO增加而IL-8含量减少; 在兔晚期动脉粥样硬化中可见IL-8和MCP-1 mRNA表达降低; 哌芳安他对血脂水平、MDA 和SOD无明显影响. 结论哌芳安他抗动脉粥样硬化机制与其升高血清NO水平, 降低TXA2含量及抑制IL-8 和MCP-1过度表达相关.

关键词: 动脉粥样硬化, 一氧化氮, 前列环素, 血栓素

Abstract: Aim To investigate the anti-atherosclerotic mechanisms of the novel compound pivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits were randomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbits in the model group and the pivanampeta-treated group were fed with hypercholesterol diet. The carotids of rabbits were cut into pieces and stained with HE.The rat or rabbit serum levels of TC, LDL-CHO, HDL-CHO, IL-8, ET-1, PGI2, TXA2, and NO were assayed. The expressions of MCP-1 and IL-8 mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted an inhibitory effect on TXA2 formation without PGI2 production in the early and later stages of atherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in the animals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In the rabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated group were decreased significantly.However, the treatment with pivanampeta had no effect on the levels of plasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease of plasma TXA2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involved in the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.

Key words: atherosclerosis, atherosclerosis, nitric oxide, nitric oxide, PGI2, PGI2, TXA2, TXA2

中图分类号:

R963

R972.6

Supporting: Foundation item: State key basic research program from the Ministry of Science and Technology of China (G1998051112).
^*Corresponding author. Tel.: 010-66932651; fax: 010-68211656

山丽梅, 张锦超, 赵艳玲, 汪海^*. 新化合物哌芳安他抗大鼠和兔动脉粥样硬化作用机理的初步研究[J]. .

SHAN Li-mei, ZHANG Jin-chao, ZHAO Yan-ling, WANG Hai^*. Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis[J]. .

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