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

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

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 0.96μ g/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× 10－6μ g/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。对

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 3 8.0μ g/mL and 0.96μ g/mL, respectively. The IC50 of T0 inhibiting LTB4 and 5－ HETE were 2.3× 10－6μ g/mL and 1.14× 10－6μ g/mL, respectively. Conclusio ns The anti inflammatory effect of Tripterygium wilfordii Hook.f. may be partl y explained by its inhibition of 5－LO activity. The anti inflammatory effect of CyA has no clinical significance since the inhibitory concentration of CyA h as exceeded its pharmacological limitation. Erythromycin has no effect on 5－LO activity.