一氧化氮合酶抑制剂对大鼠创伤性休克的治疗作用

Therapeutic efficiency of nitric oxide synthase inhibitor on traumatic shock in rats

目的 :评价选择性诱导型一氧化氮合酶 ( i NOS)抑制剂氨基胍 ( AG)和非选择性一氧化氮合酶抑制剂L 硝基精氨酸甲酯 ( L NAME)对创伤性休克的治疗效果。方法 :30只 SD大鼠制作创伤性休克动物模型。双侧股骨干砸伤后并经股动脉放血至平均动脉压 ( MAP) 35～ 45 m m Hg( 1mm Hg=0 .133k Pa) ,维持 30 m in,然后回输失血和等量的林格氏液。随机分为休克组 ( 10只 )、AG组 ( 10只 ,复苏时静脉注射 AG8mg/ kg)、L NAME组 ( 10只 ,复苏时静脉注射 L NAME8mg/ kg) ,观察休克前后血浆一氧化氮 ( NO)浓度的动态变化 ,观察 2 4h大鼠存活率 ,2 4h后留取肺、肝、肾、小肠组织 ,观察病理改变。结果 :大鼠创伤性休克后 ,血浆 NO水平明显高于休克前 ;AG组动物复苏后血浆 NO的水平明显降低 ,各脏器的病理损害亦显著减轻 ,存活率明显提高 ;L NAME组动物复苏后血浆 NO的水平也明显降低 ,各脏器的病理损害无明显变化 ,存活率无明显提高。结论 :NO在创伤性休克的病理发展过程中起着重要作用 ,应用 AG有助于创伤性休克的纠正 ,而L NAME能降低 NO的水平 ,但对休克的预后无明显改善。

Objective:To evaluate the effects of aminpguandine(AG) used as a selective inhibitor of the inducible form of nitric oxide synthase(iNOS) and NnitroLarginine methyl ester(LNAME) used as a nonselective inhibitor of nitric oxide synthase(NOS) on traumatic shock.Methods:Thirty SD(SpragueDawley) rats were used to create a animal model of traumatic shock.Both shaft of femurs were crashed and bled to mean arterial pressure of 35-45 mm Hg(1 mm Hg=0.133 kPa) via femoral artery.Hypotention was maintained 30 minutes,the shed blood was then returned,followed by an infusion with Ringer's solutions. Animals were randomly divided into three groups:traumatic shock group(n=10),AG group(AG 8 mg/kg was infused at resuscitation,n=10),LNAME group(LNAME 8 mg/kg was infused at resuscitation, n=10).Plasma levels of nitric oxide(NO) were determined before and after shock,immediately after resuscitation and 0.5,2 and 4 hours after resuscitation.The 24 hours survival rates were recorded.Lung,liver and kidney, intestine tissues were obtained 24 hours after shock for microscopic examination.Results:The plasma level of NO markerly increased after shock.The plasma level of NO markerly decreased and less tissue damages with highly survival rates in AG group.Lower plasma level of NO and survival rates and highly tissue damages were seen in LNAME group.Conclusion:NO plays an important role in development of pathologically traumatic shock.AG is beneficial of treatment in traumatic shock,but LNAME can only decrease the plasma level of NO and can not improve the outcome of shock.