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_临床医学论文.docVIP

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_临床医学论文 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_临床医学论文 【摘要】 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40 μmol/kg;抑制剂组于模型制备前24 h腹腔注射锌原卟啉(ZnPP)10 μmol/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。 【关键词】 呼吸机相关性肺损伤;血红素加氧酶-1;超氧化物歧化酶;丙二醛 　　Abstract: 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 seriou