中华皮肤科杂志 ›› 2001, Vol. 34 ›› Issue (2): 110-112.

• 论著 • 上一篇    下一篇

环孢素A、雷公藤内酯醇及红霉素与5-脂氧合酶产物的关系

孙联文, 郑家润, 陈沄, 李新宇   

  1. 中国医学科学院、中国协和医科大学皮肤病研究所 南京 210042
  • 收稿日期:2000-06-14 出版日期:2001-04-15 发布日期:2001-04-15

The Relationship Between Anti-inflammatory Effects of Antipsoriatic Drugs and 5-Lipoxygenase Products

SUN Lianwen, ZHENG Jiarun, CHEN Yun   

  1. Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China
  • Received:2000-06-14 Online:2001-04-15 Published:2001-04-15

摘要: 目的 探索环孢素A、雷公藤内酯醇及红霉素对5-脂氧合酶的影响及建立相应的药效学方法。方法 采用反相高效液相色谱法检测5-脂氧合酶产物——白三烯B4和5-羟花生四烯酸量的变化来反映该酶活性的改变。结果 环孢素A可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC50值分别为38.0和0.96μg/mL。雷公藤内酯醇(T0)可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC50值分别为2.3×10-6和1.14×10-6μg/mL。红霉素无剂量依赖性。结论 雷公藤的抗炎作用与抑制5-脂氧合酶活性有关,环孢素A的抑制浓度超出了其药理浓度,无实际意义,红霉素氧合酶活性无影响。

关键词: 花生四烯酸, 5-脂氧合酶, 白三烯B4, 羟基花生四烯酸类, 环孢素, 雷公藤内酯, 红霉素

Abstract: Objective To Investigate the effects of antipsoriatic drugs on 5.lipoxygenase(5-LO) and set up a relevant pharmacodynamic method. Methods 5-LO products, leukotriene B4 (LTB4) and 5.hydroxyeicosatetraenoic(5-HETE), we re determined by RP-HPLC to represent 5-LO activity. Results Cyclosporin A(CyA) and triptolide(T0) inhibited the production of LTB4 and 5-HETE in a dose-dependent manner, while erythromycin did without dose.dependence. The 50% inhibitory concentration values(IC50) of CyA inhibiting LTB4 and 5-HETE were 38.0μg/mL and 0.96μg/mL, respectively. The IC50 of T0 inhibiting LTB4 and 5-HETE were 2.3×10-6μg/mL and 1.14×10-6μg/mL, respectively. Conclusions The anti.inflammatory effect of Tripterygium wilfordii Hook.f. may be partly explained by its inhibition of 5-LO activity. The anti.inflammatory effect of CyA has no clinical significance since the inhibitory concentration of CyA has exceeded its pharmacological limitation. Erythromycin has no effect on 5-LO activity.

Key words: Arachidonic acid, 5-lipoxygenase, Leukotriene B4, Hydroxyeicosatet raenoic acids, Cyclosporin, Triptolide, Erythromycin