甲磺酸加贝酯在小肠缺血-再灌注损伤中的预防作用

Role of Gabexate Mesylate in Small Intestine Ischemia-Reperfusion Injury

目的观察多形核中性粒细胞(PMN)在小肠缺血-再灌注(I/R)损伤中的作用。方法采用新西兰白兔I/R损伤模型,将健康新西兰白兔随机分为I/R损伤组、药物治疗组、对照组和假手术组,各15只。阻断肠系膜上动脉(SMA)1 h后,药物治疗组立即给予颈外脉注射甲磺酸加贝酯30 mg/kg,I/R组立即给予等量0.9%氯化钠注射液。再灌注6 h后采集体静脉及门静脉血,收集支气管-肺泡灌洗液(BALF),并取肝、肺及小肠组织;假手术组仅行SMA分离术,术后6 h取标本;对照组麻醉后立即取标本。测定门、体静脉血内毒素及肺、肠组织中髓过氧化酶(MPO)舍量,观察肝组织中PMN浸润程度;肠组织病理分级,测定BALF中蛋白含量。结果肠I/R损伤可导致肝、肺、肠等远端器官中PMN聚集明显增加(P<0.05);甲磺酸加贝酯可以抑制肠I/R损伤引起的PMN聚集,减轻组织器官损伤。结论PMN在肠I/R损伤中活化聚集是导致全身炎性反应及多器官功能损伤的重要原因之一,甲磺酸加贝酯通过抑制PMN的活性及炎性介质的释放而减轻组织器官的损伤。

Objective To observe the role of polymorphonuclear neutrophils （PMN） in the small intestine ischemia-reperfusion （I/R） injury. Methods The New Zealand white rabbit I/R injury model was adopted. The healthy New Zealand white rabbits were randomly divided into the I/R injury group, drug treatment group, control group and sham operation group, 15 cases in each group. After 1 h of blocking the superior mesenterie artery （SMA）, the drug treatment group was immediately given gabexate mesylate 30 mg/kg by the ex- ternal jugular vein injection, the I/R injury group was immediately given the equal amount of 0.9% sodium chloride solution. After 6 h of reperfusion, systemic and portal vein blood was collected, the bronchoaleolar lavage fluid（BALF） was collected and the samples of liver, lungs and small intestinal tissues were taken; the sham operation group was performed only SMA separation, 6 h later the samples were taken; the samples in the control group were immediately taken after anesthesia. The observation indexes were as follows： the endotoxin content in the portosystemic vein blood and the myeloperoxidase （MPO） content in lung and intestinal tissues, observation of the PMN infiltrating degree in the liver tissue; the pathological classification of the intestinal tissues and the protein content determination of BALF. Methods The intestinal I/R damage could lead to significant increase of PMN gather in the distal organs of liver, lungs and intestine （P〈0. 05）; gabexate mesylate could restrain the bowel I/R damage induced PMN gather and reduce the injury of organs and tissues. Conclusion The activation and gather of PMN in the intestinal I/R injury is one of the important causes leading to the sys- temic inflammation reaction and the multiple organ function lesion, gabexate mesylate can reduce the damage of tissues and organs by inhibiting PMN activity and the release of inflammatory mediators.