一氧化氮和内皮素-1在内毒素休克后家兔血流动力学变化中的作用

The Roles of Nitric Oxide and Endothelin-1 in the Changes of Hemodynamics following Endotoxic Shock in Rabbits

关键词:  内毒素休克  血流动力学  一氧化氮  内皮素-1

Key words:  endotoxic shock  hemodynamics  nitric oxide  endothelin-1

摘要:

目的了解一氧化氮(NO)和内皮素-1(ET-1)在内毒素休克后血流动力学变化中的作用。方法将24只家兔随机分为3组，依次为脂多糖(LPS)对照组，氨基胍(AG，诱生型一氧化氮合酶特异性抑制剂，20 mg·kg-1)+LPS组和PD-142893(ET-1受体非选择性拮抗剂，0.02 mg·kg-1)+LPS组。测定LPS对照组给LPS前及给LPS后0.5，1，2，4，6 h各时刻的血流动力学指标及血浆NO和ET-1浓度，AG+LPS组和PD-142893+LPS组分别于LPS静注后1 h给予AG和PD-142893，测定给LPS前及给LPS后1，2，4，6 h各时刻的血流动力学指标。结果家兔LPS(1 mg·kg-1)静注后，平均动脉压(MAP)在静注LPS后0.5 h就迅速下降30.31%(P<0.05)，达到休克水平，继而保持平缓的下降趋势，至给LPS后6 h时降幅达40.61%(P<0.05)；左室最大收缩压(LVSP)、左室内压最大上升/下降速率(±dp/dt max)等指标先迅速下降然后一定的回升继而平稳下降，而左室舒张末压(LVEDP)无明显变化(P>0.05)。内毒素休克家兔血浆NO水平呈双峰变化，在给LPS后0.5 h和6 h分别升高72.50%和95.83%(P<0.05)，ET-1水平在晚期明显升高，在给LPS后6 h升高68.74%(P<0.05)。AG或PD-142893静注后各血流动力学指标均有明显改善。结论NO和ET-1的生成可能参与了内毒素休克后血流动力学的变化，通过抑制它们的作用后血流动力学有明显改善。

Abstract:

OBJECTIVE To explore the roles of nitric oxide(NO) and endothelin-1(ET-1) on the changes of hemodynamics following endotoxic shock in rabbits. METHODS 24 rabbits were divided into 3 groups: LPS control group, aminoguanidine (AG, specific inhibitor of inducible nitric oxide synthase, 20 mg·kg-1) +LPS group, PD-142893 (nonselective inhibitor of ET-1 receptors, 0.02 mg·kg-1)+ LPS group. Hemodynamic parameters and serum concentration of NO and ET-1 were monitored at baseline and 0.5, 1, 2, 4, 6 h after LPS injection in LPS control group. AG and PD-142893 were administrated at 1 h after LPS injection in AG+LPS group and PD-142893+LPS group. The hemodynamic parameters were monitored at baseline and 1, 2, 4, 6 h after LPS injection. RESULTS After LPS(1 mg·kg-1) injection, mean artery pressure (MAP) was decreased quickly and decreased 30.31% (achieved shock) at 0.5 h after LPS injection(P<0.05), then decreased steadily and decreased 40.61% at 6 h after LPS injection(P<0.05); maximum left ventricle systolic pressure (LVSP), maximum increase and decrease rate of left intraventricular pressure (±dp/dt max), were also decreased quickly at the early stage after LPS injection and had a transient increase a little later, then kept on decreasing smoothly; while left ventricle end-diastolic pressure (LVEDP) had no significant changes(P>0.05). After LPS injection, NO serum concentration presented double hump change, increased 72.50% and 95.83% respectively at 0.5 h and 6 h after LPS injection(P<0.05); ET-1 was increased significantly in the late stage and increased 68.74% at 6 h after LPS injection(P<0.05). Both AG and PD-142893 administration significantly improved hemodynamic parameters. CONCLUSIONS The production of NO and ET-1 may participate in the changes of hemodynamics following endotoxic shock. Inhibition of NO and ET-1 could significantly improve hemodynamic parameters.