大鼠血红素加氧酶-1表达对呼吸机相关性肺损伤时SOD、MDA的影响

The effect of HO-1 expression on SOD and MDA in ventilator-induced lung injury in rats

目的以大鼠呼吸机相关性肺损伤(VILI)为模型,用血晶素(hemin)诱导大鼠血红素加氧酶-1(HO-1)表达,观察VILI时超氧化物歧化酶(SOD)和丙二醛(MDA)活性变化及HO-1对SOD和MDA的影响,探讨在VILI过程中的抗氧化应激保护作用及其机制。方法32只雄性SD大鼠随机分成4组(每组n=8):对照组只做气管切开术,保留自主呼吸;模型组气管切开后行机械通气4 h;诱导剂组于模型制备前24 h腹腔注射血晶素40μmol/kg;抑制剂组于模型制备前24 h腹腔注射锌原卟啉(ZnPP)10μmol/kg。机械通气4 h后处死大鼠,收集肺组织和支气管肺泡灌洗液(BALF)标本,测定BALF中总蛋白含量,肺组织湿/干重比值(W/D),肺组织LDH、SOD活性和MDA含量,检测肺组织HO-1蛋白表达,光镜下行肺组织病理学观察。结果与对照组相比,模型组大鼠肺组织病理损伤严重,肺W/D、BALF中总蛋白、LDH活性均明显增加,VILI模型复制成功。与模型组比较,诱导剂组肺组织HO-1表达增加,肺组织病理损伤明显减轻,SOD活性明显增加而MDA含量明显下降,用ZnPP抑制HO-1表达,此种保护作用消失。结论血晶素诱导大鼠HO-1表达可以增加SOD活性,降低MDA含量,减轻肺的氧化应激损伤,降低VILI的程度。

Objective To observe the variations in superoxide dismutase（SOD） activity and malondialdehyde（MDA） levels in ventilator-induced lung injury（VILI） and the effects of HO-1 expression on SOD and MDA with the establishment of rat model of VILI and the induction of heme oxygenase-1 expression by hemin,and to investigate the protective effect and the underlying mechanism of anti-oxidative stress in VILI.Methods 32 male Sprague-Dawley rats were randomized into 4 groups： control group（tracheotomy only,with spontaneous breathing retained）,model group（tracheotomy followed by 4 h of mechanical ventilation）,inducer group（intraperitoneal injection of hemin 40 μmol/kg 24 h before model establishment）,suppressor group（intraperitoneal injection of ZnPP 10 μmol/kg 24 h before model establishment）.4 h after mechanical ventilation,the rats were sacrificed and the lung tissue and samples of bronchoalveolar lavage fluid（BALF） were collected for determination of total protein in BALF,wet-to-dry weight ratio（W/D） of lungs,LDH assaying and the activity of SOD and MDA of lung tissue,detection of lung tissue HO-1 protein expression,and observation of histopathological changes of lungs by light microscopy.Results Compared with the control group,rats in the model group had serious lung histopathological injury and marked increase in W/D of lungs,total protein in BALF and LDH activity,respectively,which suggested the successful establishment of VILI model.In the inducer group,as compared to the model group,HO-1 expression level increased and the lung histopathological injury was significantly attenuated,SOD activity significantly increased while MDA content significantly decreased.With the inhibition of HO-1 expression by ZnPP,this protective effect was reversed.Conclusion Hemin-induced HO-1 expression can increase SOD activity,decrease MDA content,alleviate oxidative stress injury to lung tissues and reduce the extent of VILI.