一氧化氮合酶抑制剂对重度失血性休克的治疗效果

Effects of nitric oxide synthases inhibitor on severe hemorrhagic shock

目的 评价选择性诱导型一氧化氮合酶 (iNOS)抑制剂氨基胍 (AG)和非选择性一氧化氮合酶抑制剂L N 位硝基精氨甲酯 (L NAME)对重度失血性休克的治疗效果。方法 40只大白兔按照Wiggers改良法制作失血性休克模型 ,经股动脉放血至MAP 30～ 35mmHg ,维持 12 0min ,然后回输失血和等量的林格氏液。随机分为休克组 (14只 )、AG组 (14只 ,复苏时静脉注射AG 2 0mg/kg)、L NAME组 (12只 ,复苏时静脉注射L NAME 30mg/kg) ,观察休克前后血浆内毒素、TNFα、NO浓度的动态变化、2 4h和 48h存活率 ,48h后留取肺、小肠、肝、肾组织 ,观察病理改变。结果 动物失血性休克后 ,血浆内毒素、TNFα、NO水平明显高于休克前 ;AG组动物复苏后血浆内毒素、TNFα、NO的水平明显降低 ,各脏器的病理损害亦显著减轻 ,动物的存活率明显提高。结论 内毒素血症、TNFα、NO在失血性休克的病理发展过程中起着重要作用 ,应用AG有助于顽固性休克的纠正 ,而L NAME对休克的预后无改善。

Objective To evaluate the effects of aminoguandine(AG) used as a selective inhibitor of the inducible isoform of nitric oxide synthase(iNOS) and L NAME used as a non selective inhibitor of nitric oxide synthase(NOS) on severe hemorrhagic shock Methods Forty rabbits were bled to mean arterial pressure of 4 4 66 kPa via femoral artery Hypotention was maintained for 120 min, the shed blood was then returned, followed by an infusion with Ringer′s solutions Animals were randomly divided into three groups: hemorrhagic shock group (n=14), AG group (AG 20mg/kg was infused intravenously ,n=14), L NAME group (L NAME 30mg/kg was infused intravenously with ,n=12) Plasma levels of endotoxin, tumor necrosis factor(TNFα) and nitric oxide (NO) were determined before and after shock, immediately after resuscitation and 0 5h, 2h, 4h after resuscitation The 24h and 48h survival rates were recorded Lung, intestine, liver and kidney tissues were obtained 48 h after shock for microscopic examination Results The plasma endotoxin, TNFα and NO levels markedly increased and were kept at high levels after shock Lower plasma levels of endotoxin TNFα and NO, less tissue damages and high survival rates were observed in AG group as compared with those in L NAME group and shock group Conclusions The endotoxin,TNFα and NO play an important role in the development of irreversible shock AG is beneficial in the treatment of hemorrhagic shock, while L NAME does not improve the outcome of shock