银杏内酯拮抗血小板活化因子对豚鼠肺条作用的实验研究

Experimental Study on Antagonism of Ginkgolides Against Effect of Platelet-Activating Factor on Lung Strip of Guinea Pigs

观察银杏内酯拮抗血小板活化因子（ＰＡＦ）加血小板能收缩豚鼠肺条的作用和桔抗ＰＡＦ破坏β－肾上腺素受体的作用。方法：对离休豚鼠肺条进行张力测定。结果：ＰＡＦ加入血小板孵化液后能引起豚鼠肺条的强烈收缩，５０％抑制浓度（ＩＣ（５０））达到４．６９×１０（－７）ｍｏｌ／Ｌ，而单纯血小板溶液的肺条收缩作用则相对较弱，ＩＣ（５０）仅为６．６６×１０（－４）ｍｏｌ／Ｌ，两组差异显著（Ｐ＜０．０５）；预先在血小板孵化液中加入银杏内酯，则ＰＡＦ和血小板混合液的肺条收缩作用明显减弱（Ｐ＜０．０５）。ＰＡＦ能减少肺组织β－肾上腺素受体的数量，使β－受体激动剂的舒张作用减弱，５０％有效浓度（ＥＣ（５０））由１．３８×１０（－６）ｍｏｌ／Ｌ增至６．２５×１０（－６）ｍｏｌ／Ｌ（Ｐ＜０．０５），ＰＡＦ的这一作用同样能被银杏内酯拮抗（Ｐ＜０．０５）。结论：银杏内酯是一种有希望的ＰＡＦ拮抗剂，有可能用于支气管哮喘的治疗。

To investigate the action of ginkgolides antagonizing the contraction of guinea pigs’ lung strip induced by the mixture of platelet-activating factor(PAF)and platelets and its effect of preventing the PAF caused damage of β-adrenergic receptors. Methods: The contraction of guinea pigs’ isolated lung strip was measured. Results:The mixture of PAF and platelet could prepuce a serious contraction of lung strip, the IC50 reached 4.69×10-7mol/L, while the contraction induced by PAF alone was relatively mild, its IC50 only 6. 66×10-4 mol/L, the difference between them was significant(P＜0. 05). When the platelets were preincubated with ginkgolides for 10 minutes in Tris-Tyrede’s buffered saline, the effects of PAF and platelets mixture were significantly inhibited(P＜0. 05). Exposure of guinea pigs’ lung strip to PAF in vitro resulted in a loss of β-adrenergic receptors and weakened its respones to isoproterenol, a receptor activating factor, the EC50 would be increased from 1. 38×10-6 mol/Lto 6. 25×10-6 mol/L, P＜0. 05. This effect of PAF could also be inhibited by ginkgolides (P＜0. 05 ). Conclusion:Ginkgolides is a promising PAF antagonist, and might be used in treating bronchial asthma.