肝缺血再灌注后肺损伤机制及乌司他丁保护作用的实验研究

Effects of ulinastatin on lung injury after hepatic ischemia reperfusion in rabbits

目的研究肝缺血再灌注后肺损伤的机制以及乌司他丁的保护作用。方法新西兰白兔24只,随机分为3组,每组8只。假手术组:麻醉后分离肝门,游离肝动静脉,关腹,120 min后处死。缺血再灌注组:夹闭左侧叶、左中央叶、右中央叶的血管,缺血60 min后再灌注60 min后立即处死。乌司它丁组同缺血再灌注组制作部分肝缺血再灌注模型,但于阻断前15 min注射乌司它丁2万U／kg。测定阻断前(T0)、阻断50 min(T1)、再灌注10 min(T2)、再灌注60 min(T3)四个时点动脉血压、动脉血血气分析和TNF-α、IL-8水平。肝肺病理切片光镜观察、肺干湿重比、肺灌洗液蛋白含量及磷脂水平、肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力、髓过氧化物酶(MPO)活力、肺组织SP-A tuRNA及SP-A蛋白表达水平。结果病理结果显示,乌司它丁组缺血再灌注肺损害较轻。缺血再灌注组和乌司它丁组pH阻断后降低,TNF-α和IL-8升高,TNF-α、IL-8水平、干湿重比、MDA、MPO高于假手术组,灌洗液蛋白浓度、PC、PG含量、SOD、SP-A蛋白表达低于假手术组(P< 0．05),而乌司它丁组各项结果要好于缺血再灌注组(P<0．05)。结论肝缺血再灌注会导致肺损伤,缺血前给予乌司它丁可以减轻肺损伤。

Objective To explore the mechanisms of lung injury after hepatic ischemia reperfusion and the protect effects of ulinastatin. Methods Twenty-four new Zealand rabbits were randomly divided into 3 groups. Sham operation group （ n = 8 ）. Hepatic isebemia reperfusion group （ n = 8 ）, with 60 min reperfusion after 60 min occlusion of left lateral lobe,left central lobe and right central lobe;ulinastatin group （ n = 8 ） ： intravenous infusion of ulinastatin 20 000 U/kg 15 min before isehemia. Mean blood pressure, arterial blood gas analysis, concentration of plasma TNF-α and IL-8 were measured before occlusion （T0 ） ,50 min after occlusion（ T1 ） , 10 min after reperfusion （ T2 ） , 60 min after reperfusion （ T3 ）. Hepatic and lung pathological section,lung D/W ratio, concentration of protein and phospholipids in BALF,content of MDA, activity of SOD and MPO,expression of SP-A mRNA and SP-A protein in lung were observed. Results By lung pathological examination,lung damage was less severe in ulinastatin group, pH were lower and level of plasma TNF-α and IL-8 were higher than before occlusion; level of plasma TNF-α and IL-8, lung D/W ratio, MDA and MPO were higher than sham operation group; concentration of protein, PC and PG in BALF, SOD and expression of SP-A protein in lung were lower than sham operation group（P 〈 0. 05 ）. The results of ulinastatin group were better than those of hepatic isehemia reperfusion group （P 〈 0.05 ）. Conclusion Ulinastatin ameliorates lung injury caused by hepatic isehemia reperfusion.