缺血预处理对大鼠肠缺血再灌注诱发肺损伤的保护作用

Protective Effect of Ischemic Preconditioning on Lung Injury Induced by Intestinal Ischemia/Reperfusion in Rats

目的探讨肠缺血预处理对大鼠肠缺血再灌注（intestinal ischemia-reperfusion group,IIR）诱发肺损伤的保护作用及其机制。方法雄性SD大鼠24只,体重210~260g,随机分为4组,每组6只：正常对照组（Sham组）、肠缺血再灌注组（IIR组）、肠缺血预处理组（ischemic preconditioning,IPC组）和锌原卟啉（zinc protoporphyrin,ZnPP）＋肠缺血预处理组（ZnPP组）。通过结扎/放松肠系膜上动脉的方法建立大鼠肠缺血再灌注损伤模型。再灌注结束后,检测肺组织血红素加氧酶1（heme oxygenase-1,HO-1）的活性、肺组织湿干重比、丙二醛（malondialdehyde,MDA）含量和超氧化物歧化酶（superoxide dismutase,SOD）活性,检测血清肿瘤坏死因子α（tumor necrosis factor alpha,TNF-α）和白细胞介素6（interleukin-6,IL-6）水平的变化,光镜下观察肺组织的结构变化。结果与IIR组比较,IPC组肺组织HO-1活性增强,肺组织湿干重比、MDA含量和细胞因子TNF-α和IL-6水平降低,SOD活性增加,肺组织损伤较轻（P〈0.01）,ZnPP组HO-1活性降低,肺组织湿干重比、MDA含量和细胞因子TNF-α和IL-6水平增加,肺组织损伤较重（P〈0.05或0.01）,SOD活性差异无统计学意义（P〉0.05）;与IPC组比较,ZnPP组肺组织HO-1活性降低,肺组织湿干重比、MDA含量和细胞因子TNF-α和IL-6水平增加,SOD活性降低,肺组织损伤较重（P〈0.01）。结论缺血预处理对肠缺血再灌注诱发肺损伤的保护作用是通过诱导HO-1活性增加实现的。

Objective To investigate the effect of ischemic preconditioning（IPC） on lung injury induced by intestinal ischemia/reperfusion（IIR） in rats and the mechanism.Methods Twenty-four male SD rats were randomly divided into 4 groups（n=6 each）： control group undergoing sham operation,IIR group,ischemic preconditioning（IPC） group and the group receiving heme oxygenase-1（HO-1） inhibitor zinc protoporphyrin（ZnPP） 10 mg/kg one day before IPC（ZnPP group）.The superior mesenteric artery（SMA） was exposed and occluded for 30 minutes of ischemia,then the clamp was removed for 180 minutes of reperfusion to establish a model of IIR injury.Ischemic preconditioning was induced by 3 episodes of 5 minutes occlusion of SMA at 5 minutes intervals before intestinal ischemia.The superior mesenteric artery was exposed but not occluded in control group.At the end of 180 minutes reperfusion,lung tissue samples were obtained to assess lung tissue HO-1 enzyme activity,lung tissue wet/dry ratio,malondialdehyde（MDA） level,superoxide dismutase（SOD） activity,histological changes of lung was observed,and serum tumor necrosis factor alpha（TNF-α） and interleukin-6（IL-6） concentrations were examined by enzyme-linked immunosorbent assay.Results Compared with IIR group,in IPC group,lung tissue HO-1 enzyme activity and SOD activity were significantly increased（P0.01）,and lung wet/dry ratio,lung tissue MDA content,serum TNF-α and IL-6 concentrations and lung injury were significantly decreased（P0.01）;in ZnPP group,lung tissue HO-1 enzyme activity was decreased（P0.05）,lung wet/dry ratio,lung tissue MDA content,serum TNF-α and IL-6 concentrations and lung injury were increased（P0.05 or 0.01）,and lung tissue SOD activity had no difference（P0.05）.Compared with group IPC,in ZnPP group,lung tissue HO-1 enzyme activity and SOD activity were decreased（P0.01）,and lung wet/dry ratio,lung tissue MDA content,serum TNF-α and IL-6 concentrations and lung injury were increased（P0.01）.Conclusion IPC can protect against IIR induced lung injury by increasing HO-1 enzyme activity