犬重症急性胰腺炎血浆内毒素和炎性介质的变化及血小板活化因子受体拮抗剂的干预  

Dynamic changes of plasma endotoxin and inflammatory mediators in dogs with severe acute pancreatitis and intervention with platelet activating factor receptor antagonist

作　　者：夏时海[1] 赵晓晏[2] 郭萍[2] 张伟龙[1] 任万英[1] 王素莉[1] 

机构地区：[1]武警医学院附属医院消化内科,天津300162 [2]第三军医大学附属新桥医院消化内科

出　　处：《武警医学》2002年第10期581-584,共4页Medical Journal of the Chinese People's Armed Police Force

摘　　要：目的　动态观察重症急性胰腺炎 (Severeacutepancreatitis,SAP)后血浆内毒素 (Lipopplysaccharide,LPS)、血小板活化因子 (Platelet-activatingfactor,PAF)、磷脂酶A2 (PhospholipaseA2 ,PlA2 )和中性粒细胞弹性蛋白酶 (Neutrophilelastase ,NE)的变化 ,以及一种新型PAF受体拮抗剂 -E 5 880的干预效果。方法　选健康杂种犬 2 8只 ,体重 10～ 15kg,雌雄不限 ,随机分为 5组 :假手术组 (n=5 ) ,SAP组 (n =6 ) ,二甲亚砜 (DMSO)组 (n =5 ) ,SAP +E 5 880预防组 (n =6 )和SAP +E 5 880治疗组 (n =6 )。用 5 %牛磺胆酸钠混合液诱导SAP组 ,以 0 9%NaCl磷酸盐缓冲液或DMSO取代 5 %牛磺胆酸钠混合液诱导假手术对照组和DMSO对照组。SAP +E 5 880预防组在SAP诱导前 30min静推E 5 880 ,剂量 10mg/kg。SAP +E 5 880治疗组在SAP诱导后6h静推E 5 880 ,剂量 10mg/kg ,此后按 5mg/kg每 12h静推 1次。结果　SAP导致血浆LPS、PAF、PLA2 、NE水平明显升高。预防或治疗性给予E 5 880均可显著降低SAP后LPS、PAF、PLA2 、NE水平 ,且血浆PAF水平的变化与血浆LPS、PLA2 、NE水平呈显著正相关 (P <0 0 1)。结论　SAP可引起LPS、PAF、PLA2 、NE等炎性介质大量释放 ,而这些炎性介质正是介导SAP后全身性炎症反应甚至多器官功能损害?Objective To explore the dynamic changes of levels of plasma endotoxin and inflammatory mediators such as platelet-activating factor (PAF),phospholipase A 2(PLA 2) and neutrophil elastase (NE) in the onset and course of severe acute pancreatitis (SAP),and the offectiveness of intervention with PAF receptor antagonist E 5880,a new potent PAF receptor antagonist.Methods Twenty-eight dogs weighing 10～15 kg were divided randomly into five groups:group Ⅰ(n=5),sham-operated control;group Ⅱ(n=6),SAP-control;group Ⅲ (n=5) with DMSO-control;group Ⅳ (n=6) and group Ⅴ (n=6).pre-and posttreatment E 5880.Anesthetized dogs were subjected to SAP induced by injectoin of compouind solution of 5% sodium taurocholate and trypsin into the main pancreatic duct.Systemic venous blood was collected for the determinations of LPS,PAF,PLA 2,and NE.Results The activities of NE and PLA 2 and the levels of PAF,LPS in plasma increased significantly in SAP.The pre-and posttreatment with E 5880 in SAP remarkably reduced the levels of plasma LPS,PAF,NE and PLA 2.The changes of plasma PAF were significantly correlated with those of plasma LPS,PLA 2 and NE (P<0.01).Conclusions SAP can induce the release of a great deal of inflammatory mediators such as LPS,PAF,PLA 2 and NE,by which systemic inflammatory response syndrome (SIRS) and even multiple organ injuries following SAP are brought about.The pre-or posttreatment with E 5880 significantly reduces the high levels of plasma LPS,PAF,PLA 2 and NE following SAP and plays an important role in protecting extra-pancreatic organ injuries brought about by inflammatory mediators in SAP.

关 键 词：重症急性胰腺炎 血小板活化因子 内毒素 中性粒细胞弹性蛋白酶 磷脂酶A2 E 5880 

分 类 号：R576.02[医药卫生—消化系统]