一氧化氮合酶抑制剂对创伤性休克的干预作用

The interventional effect of nitric oxide synethase inhibitors on traumatic shock

目的:评价选择性诱导型一氧化氮合酶(iNO)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)对创伤性休克的治疗效果.方法:40只Wistar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)35～45mmHg(4.67～6.00kPa),维持30min,然后回输失血和等量的林格式液.随机分为休克组(10只),AG组(根据复苏时静脉注射AG含量为10,50mm/kg.则分为AG Ⅰ,AGⅡ各10只),L-NAME组(10只,复苏时静脉注射L-NAME 10mg/kg),观察休克前后血浆NO浓度的动态变化及24h大鼠存活率.并留取肺、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各组动物复苏后血浆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,AGⅡ组效果最好;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改善;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 a selective inhibitor of inducible nitric oxide synthase（iNOS）-aninoguanicIine（AG） and a non-selective inhibitor of nitric oxide synthase- （NOS）L-NAME on traumatic shook in rats. Methods： Animal models of traumatic shock were estalolished in 40 Wistar rats following fractures in both femur shafts and subsequent depletion until the mean arterial pressure in the femoral artery dropped to 35 to 45mmHg（4. 67～6. 00KPa）. Hypotension was maintained for 30min Before the collected Blood was infused back into the rats supplemented with Rinser＇s solution of the same volume,the rat models were then randomly divided into 3 groups： traumatic shock group （n= 10）;AG group（which was subdivided into AG Ⅰ, AG Ⅱ groups ,each oonsisting of 10 rats and receiving 10 and 50mg/kg AG ininfuslon respeotlvely during resusoltaiton）,and L-NAME group（with 10mg/kg L-NAME infusion during resusoltation,n= 10）. Plasma NO level was determined before and after shock, Immediately after resusoltaion and 0. 5,2,4h after resuscitation ,and the survival rate within 24h were recorded with tissue samples of the luns, liver, kidney and Intestine obtained 24h after shock for microsooplc exarnlnation. Results：Plasma NO level was Increased markedly after traumatic shock in the rat models. In the AG Ⅱ group,the elevated NO level following the shock was obviously reduced after resuscitaiton with less tissue damases and higher survival rate, as oompared with the other groups. The best proteotive effect asainst traumatic shock was observed in AG Ⅱ Stoup, In spite of obvious decrease of plasma NO level after resusoitation,L-NAME exhibited little efficacy In allevlating the tissue damages in the orsans and hence failed to improve the surviat rate of rats. Conclusion：NO plays an important role in the patholosioal process of traumatic shock, and the application of AG may improve the condition, L-NAME can decrease plasma NO level after resusoitation,but fail to improve the outcome of traumatic shock in rats.