PAF受体拮抗剂苦银杏内酯B对内毒素休克不同介质的作用

Effects of PAF Receptor Antagonist Gingkolide B on Inflammatory Mediators During Endotoxic Shock

目的：研究内毒素休克时ＰＡＦ对ＴＮＦ、ＮＯ２／ＮＯ３的影响，探讨其可能的机理。材料与方法：将家兔随机分为５组，Ⅰ组：假手术对照组ｎ＝８；Ⅱ组：低剂量内毒素休克组ｎ＝１５，Ｅ．ｃｏｌｉ内毒素静脉一次性注射２００μｇ／ｋｇ；Ⅲ组：高剂量内毒素休克组ｎ＝１５，内毒素静脉一次性注射３００μｇ／ｋｇ；Ⅳ（或Ⅴ）组：低（或高）剂量内毒素并苦银杏内酯Ｂ预处理组ｎ＝１５，苦银杏内酯Ｂ５ｍｇ／ｋｇｉｐ注射，１０分钟后再分别静脉注射内毒素２００或３００μｇ／ｋｇ。于给药前、给药后即刻、３０、６０、１８０、３００、４８０分钟取血，测定血ＰＡＦ、ＴＮＦ、ＮＯ２／ＮＯ３。结果：内毒素休克时血浆ＰＡＦ、ＴＮＦα、ＮＯ２／ＮＯ３等均显著升高，且与内毒素的剂量密切相关。苦银杏内酯Ｂ预处理后对ＰＡＦ、ＴＮＦα的水平没有明显影响；对血浆ＮＯ２／ＮＯ３的升高有明显的抑制作用。苦银杏内酯Ｂ预处理后可使动物的存活率有较大的提高。结论：ＰＡＦ受体拮抗剂苦银杏内酯Ｂ可选择性地影响休克介质（如ＰＡＦ、ＴＮＦ、ＮＯ２／ＮＯ３等）的释放，提高动物的存活率。

Purpose:The experiment was designed to investigate the effects of PAF receptor antagonist Ginkgolide B on plasma PAF,TNFα and NO2/NO3 during endotoxic shock.Materials and methods:Rabbits were randomly divided into 5 groups,Ⅰ:shamoperated group n=8;Ⅱ:shock group treated with low dose endotoxin (200μg/kg iv) n=15;Ⅲ:shock group treated with high dose endotoxin (300μg/kg iv) n=15;Ⅳ(orⅤ):shock group pretreated with 5mg/kg ip ten minutes before low (or high does) endotoxin treatment.Samples were taken according time courses of baseline,15,30,60,180,300 and 480 minutes separately.Plasma levels of PAF,TNFα and NO2/NO3 were determined.Results:Plasma levels of PAF,TNFα and NO2/NO3 increased remarkably during endotoxic shock,and the increase was closely related to the doses of endotoxin.Pretreatment with Ginkgolide B could not influence the changes of plasma PAF or TNFα.But it could effectively inhibit the increase of NO2/NO3 induced by either low or high dose of endotoxin.Moreover,pretreatment with Ginkgolide B could increase the animals' survival rate.Conclusion:PAF receptor antagonist Ginkgolide B may selectively influence the release of mediators during shock states,and pretreatment with it could increase the animals' survival rate.