金属硫蛋白在大鼠肺缺血/再灌注损伤中的作用

Effects of metallothionein in lung ischemia/reperfusion injury in rats

目的:观察硫酸锌诱导金属硫蛋白在肺缺血/再灌注损伤中的作用及其机制。方法:健康雄性SD大鼠24只,随机分为对照组(C组)、缺血/再灌注组(I/R组)和硫酸锌+缺血/再灌注组(MT组)。对比观察各组肺组织中金属硫蛋白(MT)的含量,血清中丙二醛(MDA)含量,超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活力的变化;原位缺口末端标记法(TUNEL)检测肺组织细胞凋亡情况,透射电镜观察肺组织超微结构的改变。结果:I/R组与C组相比,肺组织中MT的含量显著下降,MDA含量、MPO活力明显升高,SOD活力明显下降(P<0.05或P<0.01),肺组织原位细胞凋亡检测示I/R组凋亡指数(AI)显著高于C组,肺组织超微结构发生异常改变;MT组与I/R组相比肺组织中MT的含量显著升高(P<0.01),MDA含量、MPO活力明显下降,SOD活力明显升高(P<0.05或P<0.01),AI显著低于I/R组,肺组织超微结构异常改变有所减轻。结论:金属硫蛋白能减轻肺缺血/再灌注损伤,其机制可能通过减轻脂质过氧化反应及中性粒细胞聚集,使肺组织细胞凋亡减少。

Objective：To observe the effects of metallothionein in lung ischemia/reperfusion injury and its mechanism.Methods：Adult male Sprague-Dawley rats were randomly divided into 3 groups based upon the intervention（n =8）：control group（C）,LIR group（I/R）,LIR＋ZnSO4 group（MT）.At the end of the experiment,the content of metallothionein in lung tissuewas was tested;the content of malondialdehyde（MDA） in serumt,he activity of superoxide dismutase（SOD） and myeloperoxidase（MPO）were tested;the pneumocyte apoptosis index（AI） was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling（TUNEL）;ultrastructural changes of lung tissue were observed under transmission electron microscope.Results：Metallothionein induced by ZnSO4 could significantly attenuate the MDA level,MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells vs.the I/R group（all P 〈0.01）,There were abnormal changes of the ultrastructure in I/R,and markedly reversed in MT group.Conclusion：Metallothionein may attenuate lung ischemia/reperfusion injury by inhibiting pneumocyte apoptosis and by inhibiting oxidant generation and neutrophils filtration.