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一氧化氮合酶抑制剂对大鼠创伤性休克的干预作用 被引量:5

Intervention with nitric oxide synthase inhibitors for traumatic shock in rats
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摘要 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-硝基精氨酸甲酯(L-NAME)对创伤性休克的治疗效果.方法用44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 mmHg(4.67~6.00kPa),维持30min,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(根据复苏时静脉注射AG含量为2、8、60 mg/kg@b.w.则分为AGI、AGⅡ、AGⅢ组,各8只)、L-NAME组(10只,复苏时静脉注射L-NAME 8 mg/kg@b.w.),观察休克前后血浆NO浓度的动态变化及24 h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,并且AGⅢ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: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 a selective inhibitor of inducible nitric oxide synthase (iNOS) aminoguanidine (AG) and a non-selective inhibitor of nitric oxide synthase (NOS) N(G)-nitro-L-arginine methylester (L-NAME) on traumatic shock in rats. Methods Animal models of traumatic shock were established in 44 Sprague-Dawley rats following fractures in both femur shafts and subsequent depletion until the mean arterial pressure in the femoral artery dropped to 35 to 45 mmHg(4.67~6.00 kPa). Hypotension was maintained for 30 min before the collected blood was infused back into the rats supplemented with Ringer's solution of the same volume. The rat models were then randomly divided into 3 groups, namely traumatic shock group (n=10), AG group (which was subdivided into AGⅠ, AGⅡ, and AGⅢgroups, each consisting of 8 rats and receiving 2, 8, and 60 mg/kg·b.w AG infusion respectively during resuscitation), and L-NAME group (with 8 mg/kg·b.w L-NAME infusion during resuscitation, n=10). Plasma NO levels were determined before and after shock, immediately after resuscitation and 0.5, 2, 4 h after resuscitation, and the survival rates within 24 h were recorded with tissue samples of the lung, liver, kidney and intestine obtained 24 h after shock for microscopic examination. Results Plasma NO level was seen to increase markedly after traumatic shock in the rat models. In the 3 AG groups, the elevated NO levels following the shock were obviously reduced after resuscitation with less tissue damages and higher survival rates, as compared with the other 2 groups. The best protective effect against traumatic shock was observed in AGⅢgroup. In spite of obvious plasma NO level-lowering effect after resuscitation, L-NAME exhibited little efficacy in alleviating the tissue damages in the organs and hence failed to improve the survival rate of the rats. Conclusions NO plays an important role in the pathological process of traumatic shock, and the application of AG may improve the con
出处 《第一军医大学学报》 CSCD 北大核心 2003年第4期306-309,共4页 Journal of First Military Medical University
基金 广东省自然科学基金(001048)~~
关键词 创伤性休克 一氧化氮合酶抑制剂 氨基胍 L-硝基精氨酸甲酯 动物实验 shock, traumatic nitric oxide synthase inhibitor aminoguanidine N(G)-nitro-L-arginine methylester mean arterial pressure
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参考文献1

  • 1赵克森,金丽娟主编..休克的细胞和分子基础[M].北京:科学出版社,2002:342.

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