内皮素受体拮抗剂对兔肺血栓栓塞症模型的影响  

Effects of endothelin antagonist on acute pulmonary thromboembolism caused by autologous blood blots in rabbits

作　　者：罗琴[1] 王辰[2] 庞宝森[2] 秦志强[2] 杨晓红[1] 黄亦芬[3] 

机构地区：[1]新疆自治区人民医院呼吸内科,新疆乌鲁木齐830054 [2]首都医科大学附属北京朝阳医院北京呼吸病研究所 [3]新疆医科大学第一附属医院呼吸内科

出　　处：《中国呼吸与危重监护杂志》2004年第5期274-277,共4页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家"十五"攻关课题基金资助项目 (2 0 0 1BA70 3B13 )

摘　　要：目的　观察内皮素受体拮抗剂 (ETA)PD14 5 0 6 5对家兔肺血栓栓塞症 (PTE)内皮素 1(ET 1)、一氧化氮 (NO)、血管性血友病因子 (vWF)、血压和血气指标的影响 ,探讨治疗PTE的新方法。方法　健康雄性新西兰大耳白兔 2 4只 ,随机分为三组 ,每组 8只 :对照组 (NC组 )、单纯栓塞组(PTE组 )和内皮素受体拮抗剂组 (ETA组 )。除NC组外 ,其余二组每只家兔均经股静脉注入 2 5个栓子 ,ETA组每只动物静脉注射PD14 5 0 6 5 0 1mg/kg。于栓塞前 ,栓塞后 1、2及 4h动态监测ET 1、NO、vWF、血压及血气变化。结果　 (1)ETA组ET 1低于PTE组 ;PTE组NO低于NC组 ,ETA组NO则高于PTE组 (P <0 0 1) ;PTE组vWF高于NC组 ,ETA组vWF则低于PTE组 (P <0 0 1) ;(2 )ETA组PaO2 高于PTE组 ,PTE组PaO2 则低于NC组 (P <0 0 1) ;ETA组收缩压和舒张压高于PTE组。结论ETA通过阻断ET 1,可舒张肺血管 ,降低血小板黏附血管壁的能力 ,阻止血栓增大 ,改善肺血管的血流动力学及血气交换功能 ,并能稳定体循环压。ETA可能为治疗PTE的一种新的、更有效的方法。Objective To study the effects of PD145065,a novel nonselective ET A/ET B receptor antagonist(ETA),on the expressions of endothelin-1(ET-1),nitric oxide(NO),von Willebrand factor(vWF),blood pressure and arterial blood gas to explore a new therapeutic approach for pulmonary thromboembolism(PTE).Methods Twenty-four New Zealand white rabbits were randomly divided into three groups: saline control group(NC),PTE group and ETA group.The animals in different groups were treated as follows:those in NC group were injected with 5 mL NS intravenously;those in PTE group were infused with 25 thrombi via femoral vein and those in ETA group were infused with 25 thrombi via femoral vein followed by administration of PD145065 (0.1 mg/kg) dissolved in 5 mL NS via ear marginal vein.HR,BP and blood gas analysis were monitored before and 1 hr,2 hrs and 4 hrs after intervention.The blood samples were taken to detect the levels of ET-1,NO and vWF.Results The level of ET-1 in ETA group was lower than that in PTE group.The level of NO in PTE group was lower than that both in NC group and in ETA group(P<0.01).The level of vWF in PTE group was higher than that both in NC group and in ETA group(P<0.01).The level of PaO 2 in PTE group was lower than that in NC group and in ETA group(P<0.01).The levels of SBP and DBP in ETA group were higher than that in PTE group.Conclusions PD145065 can improve the function of vascular endothelia and coagulatory function through inhibition of ET-1 in PTE model,in which intervention on NO and vWF may be involved.So the oxygenation and hemodynamic disturbances resulted from PTE were ameliorated.Our data support ETA as a valuable therapeutic agent for PTE.

关 键 词：PTE ETA 内皮素受体拮抗剂 ET-1 治疗 肺血栓栓塞症 PAO2 血压 PD 肺血管 

分 类 号：R563.5[医药卫生—呼吸系统] R753[医药卫生—内科学]