重组人白介素-10对大鼠肺缺血再灌注损伤的保护作用

Protective effects of recombinant human interleukin 10 on lung ischemia-reperfusion injury in rats

目的:探讨重组人白介素-10(rhIL-10)对大鼠肺缺血再灌注损伤的保护作用及可能机制。方法:显微镜下夹闭左肺动静脉和左主支气管建立单肺缺血再灌注模型。72只Wistar大鼠随机分为对照组(Control组)、缺血再灌注组(IR组)、rhIL-10药物干预组(rhIL-10组),每组分为缺血45min、再灌注60、120min 3个时间点。每个时间点8只,共24只。按上述时间点处死收集标本,检测血浆TNF-α、丙二醛(MDA)水平,观察肺组织病理变化。结果:各组MDA在缺血45min时差异无统计学意义(P>0.05),再灌注60min和120min时IR组明显升高,而rhIL-10组虽较Control组升高,但明显低于IR组(P<0.05)。与Control组比较,IR组缺血45min时TNF-α水平明显升高(P<0.05),rhIL-10组无明显变化(P>0.05)。再灌注60min和120min时IR组TNF-α水平较Control组明显升高(P<0.05),而rhIL-10组虽较Control组显著升高(P<0.05),但明显低于IR组(P<0.05)。肺病理提示肺泡间隔及肺泡内炎性细胞浸润,肺泡腔内大量炎性细胞渗出、出血,且随着再灌注时间的延长,损伤加重。rhIL-10组病理损伤均较IR组为轻。结论:rhIL-10可能通过抑制氧自由基生成、中性粒细胞浸润、TNF-α反应对肺缺血再灌注损伤起保护作用。

AIM：To evaluate the protective effects of recombinant human interleukin 10 on lung ischemia-reperfusion injury in rats and its possible mechanisms.METHODS： Rat models of lung ischemia-reperfusion were established by clamping of the left pulmonary arteries,left pulmonary veins and left main bronchus.72 healthy Wistar rats were randomly divided into three groups： surgical control group（group Control）,ischemia-reperfusion group（group IR） and recombinant human interleukin 10 pretreated group（group rhIL-10）.Every group included 24 rats（8 rats at 45 min ischemia,60 min and 120 min reperfusion respectively）.Rats were sacrificed at relative time point collecting the plasma and lung sample.The plasma contents of malondialdehyde（MDA） and TNF-α were determined.Lung pathology were examined.RESULTS：The plasma content of MDA was not different statistically among three groups after 45 min of ischemia（P0.05）.Both group IR and group rhIL-10 showed significantly increased MDA content relative to group Control,while group rhIL-10 was lower than that of group IR after 60 min of reperfusion and 120 min of reperfusion（P0.05）.The plasma content of TNF-α in group IR was increasing significantly relative to group Control after 45 min of ischemia（P0.05）.The content of TNF-α in group rhIL-10 was not different statistically compared with group Control（P0.05）.Both group IR and group rhIL-10 showed significantly increased TNF-α content relative to group Control while group rhIL-10 was lower than that of group IR after 60 min of reperfusion and 120 min of reperfusion（P0.05）.Pathological examination showed severe polymorphonuclear leukocytes infiltration with bleeding.Group IR was worse than group rhIL-10 on the pathological examination.CONCLUSION： Pretreatment with rhIL-10 protected the lungs against ischemia-reperfusion injury possibly by suppressing PMN infiltration,reducing production of oxygen radicals,inhibiting reacting of TNF-α.