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

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。

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

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), were 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 38.0 μ g/mL and 0.96 μ g/mL, respectively.The IC50 of T0 inhibiting LTB4 and 5-HETE were 2.3× 10-6 μ g/mL and 1.14× 10-6 μ g/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.