赖氨酸氯尼辛对大鼠肺和胃组织中环氧化酶I和II的影响。

Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations.

作者信息

Franchi A M, Di Girolamo G, de los Santos A R, Martí M L, Gimeno M A

机构信息

Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 1998 Jun;58(6):421-4. doi: 10.1016/s0952-3278(98)90164-8.

DOI:10.1016/s0952-3278(98)90164-8

PMID:10189073

Abstract

Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic activity that produces minor digestive side-effects. This fact induced us to think that LC is possibly a weak COX-1 inhibitor. In order to investigate our hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and control rats. Rat lung preparations incubated with 14C-arachidonic acid synthesise mainly PGE2. LC at 2.5 and 4.1 x 10(-5) M does not modify the basal production of PGE2 (probably COX-1) but at 6.8 x 10(-5) M significantly inhibited PGE2 production (approximately 48.5% inhibition, P<0.001). On the other hand, INDO at 10(-6) inhibited the basal production of PGE2 by around 73%. In LPS-treated rats, the production of PGE2 was significantly higher than in the lungs of control rats, probably due to the induction of COX-2. The addition of LC at 2.7 and 4.1 x 10(-5) M recovered the control values of PGE2 inhibiting, probably only from COX-2 activity. LC at higher concentrations (6.8 x 10(-5) M) and INDO 10(-6) M inhibited PGE2 formed by COX-2 and also partly by COX-1 activity.

摘要

氯尼辛赖氨酸（LC）是一种具有抗炎、解热和镇痛活性的药物，会产生轻微的消化系统副作用。这一事实促使我们认为LC可能是一种弱环氧化酶-1（COX-1）抑制剂。为了验证我们的假设，我们用LC或吲哚美辛（INDO）抑制脂多糖（LPS）处理的大鼠和对照大鼠的肺和胃中的环氧化酶活性。用14C-花生四烯酸孵育的大鼠肺组织主要合成前列腺素E2（PGE2）。2.5和4.1×10（-5）M的LC不会改变PGE2的基础产量（可能是COX-1），但在6.8×10（-5）M时会显著抑制PGE2的产生（抑制约48.5%，P<0.001）。另一方面，10（-6）M的INDO抑制PGE2的基础产量约73%。在LPS处理的大鼠中，PGE2的产量显著高于对照大鼠的肺组织，这可能是由于COX-2的诱导。添加2.7和4.1×10（-5）M的LC可恢复PGE2抑制的对照值，可能仅抑制COX-2活性。较高浓度（6.8×10（-5）M）的LC和10（-6）M的INDO抑制由COX-2形成的PGE2，也部分抑制COX-1活性。