西维来司钠对肝缺血再灌注后肺损伤保护作用的实验研究

目的观察西维来司钠对家兔肝热缺血再灌注肺组织中性粒细胞浸润及IL-8表达的影响并探讨其机制。方法24只家兔被随机分为假手术组、对照组和西维来司钠治疗组，各8只，均于常温全肝门阻断25min，分别于缺血前、再灌注即刻、灌注后1、2、3、4h取血，然后处死家兔取肺组织，ELISA检测血清IL-8水平，HE染色切片观察肺组织病理变化、中性粒细胞数、肺水肿程度，免疫组化检测肺组织IL-8蛋白表达并分析血清IL-8水平与中性粒细胞数的相关性。结果假手术组血清IL-8无明显变化，肺组织未发现IL-8蛋白表达及肺水肿；治疗组IL-8峰值、肺组织中性粒细胞数、IL-8蛋白表达、肺水肿程度均低于对照组相同指标（P〈0．05），血清IL-8峰值与4h时肺组织中性粒细胞浸润数成正相关（r=0．788,P〈0．01）。结论西维来司钠可能通过抑制肺组织IL-8表达，从而抑制中性粒细胞浸润，达到减轻肝热缺血再灌注导致的肺损伤。

Effect of sivelestat sodium on lung infury in rabbits with hepatic ischemia-reperfusion

Objective To investigate the effect of neutrophil elastase inhibitor sivelestat sodium on neutrophil infiltration and IL-8 expression in lung of the rabbits with hepatic heat isehemia-reperfusion. Methods Twenty-four rabbits were randomly divided into there equal groups： sham operation group, control group and treatment group. In control and treatment group, total hepatic portal were blocked for 25 minutes under common temperature. Arterial blood were abtained before ischemia（baseline）, reperfusion O, 1, 2, 3, 4 h, respectively. ELISA method was used to test serum IL-8 level at each time point. At reperfusion 4 h, all rabbits were killed. The pathological changes of lung sections were observed with HE stain, accumulated polymorphonuclear neutrophils number and the pulmonary edema degree in lung sections was counted, the IL-8 protein expression in lung sections were investigated by immunohistochemical method. Results In sham operation group, there was no significant change of serum IL-8 level, no IL-8 protein expression or pulmonary edema were found. The peak serum IL-8 level in treatment group was sinifieantly lower than that in control group（P〈0.01）. The same result were also found in the the neutrophil infiltration and IL-8 protein expression in lung and the pulmonary edema degree between the treatment and control group （P〈0.05）. There were positive correlations between the serum IL-8 peaked level and the neutrophil infiltration number in lung at 4h reperfusion（r=0.788, P〈0.01）. Conclusion Sivelestat sodium can inhibit the IL-8 expression in lung, decrease the neutrophil infiltration in lung, and decrease the lung injury induced by hepatic ischemia-reperfusion.