血红素加氧化酶-1对呼吸机相关性肺损伤大鼠的保护作用  

Protective effect of heme oxygenase-1 on ventilator associated lung injury in rats

作　　者：王红鸾[1] 汪俊[1] 郭韶梅[1] 付强[1] 喻杰[1] 李秋根[1] 

机构地区：[1]江西省人民医院二部呼吸内科,南昌330006

出　　处：《江西医药》2015年第12期1362-1365,1368,共5页Jiangxi Medical Journal

基　　金：江西省科技厅(20111BBG70020-2);江西省自然科学基金(2011ZBAB204023)

摘　　要：目的建立呼吸机相关性肺损伤(ventilator associated lung injury,VALI)大鼠模型,了解血红素加氧化酶-1(heme oxygenase-1,ho-1)对其的影响,并探讨其作用机制。方法将30只SD大鼠随机均分为3组:对照组、氯化血红素(hemin)处理组和VALI模型组。对照组不作机械通气处理;VALI模型组行大潮气量(40ml/kg)机械通气;Hemin处理组,实验前2d,按40μmol/kg剂量腹腔注射hemin,每天2次,共2d。大鼠机械通气4h后放血处死,计算肺湿干重(W/D)比值。收集肺泡灌洗液(BALF),测定其总蛋白含量及行白细胞(WBC)计数。采用酶联免疫吸附法测定血清及BALF中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-6、IL-8及IL-10的细胞因子浓度,比色法测定血清和BALF中超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(Methane Dicarboxylic Aldehyde,MDA)浓度。结果⑴hemin处理组与对照组相比,其W/D、WBC计数、TP含量均升高(均P<0.05);与VALI模型组相比,hemin组W/D、WBC计数、TP含量均降低(均P<0.05)。⑵与对照组相比,VALI模型组大鼠BALF和血清中TNF-α、IL-6、IL-8水平和MDA活性均明显升高、而IL-10和SOD浓度则明显降低(均P<0.01)。与VALI模型组相比,hemin组BALF中TNF-α、IL-6、IL-8和MDA活性降低,IL-10和SOD浓度增高(均P<0.05)。对照组和hemin组相比,大鼠BALF中TNF-α、IL-6、IL-8水平和MDA活性均有所升高,SOD和IL-10浓度则降低(均P<0.05)。结论 hemin能够有效治疗VALI,其机制与抑制各种炎性因子、降低肺部微循环通透性及减少内脂质过氧化等有关。Objective To investigate the effect of ho-lpretreatment in a rat model of ventilator associated lung in jury（VALI） and its possible mechanisms. Methods Thirty male SD rats were randomly divided into 3 groups：control group,VALI model group,and heroin pretreatment group. The control group without mechanical ventilation;VALI model group set parameters of mechanical ventilation being tidal volume 40ml/kg;hemin pretreatment group intraperitoneal injection hemin 40μmol/kg, 2 days before the experiment, 2 times a day, a total of 2d. The animals were sacrificed by exsanguinations at the end of 4h mechanical ventilation. The lungs were removed, and the wet to dry weight ratio（W/D） was measured. Broncho alveolar lavage fluid（BLAF） was obtained for determination of total protein （TP） contents and WBC counts. The levels of TNF-α, IL-6, IL-8, IL-10, SOD and MDA in the serum and BALF were detected. Results （1）hemin treatment group compared with control gmup,W/D,WBC counts,TP content are increased （all P〈0.05）;Compared to VALI model group, W/D, WBC counts,TP content are lower in heroin treatment group （all P〈0.05）. （2）As compared with control group, the levels of TNF-α, IL-6, IL-8 and MDA in serum and BALF were significantly increased in VALI model group,but the levels of IL-10 and SOD were significantly decreased （all P〈0.01）. Compared with the VALI model group,the levels of TNF-α,IL-6,IL-8 and MDA in serum and BALF were decreased,but IL-10 and SOD were increased in hemin treatment group （all P〈0.05）. Compared with control group,the levels of TNF-α,IL-6,IL-8 and MDA in serum and BALF was increased,the concentration of SOD and IL-10 is lower in hemin treatment group （all P〈0.05）. Conclusion Pretreatment with hemin can effective treatment VALI in rats by suppressing the generation of oxygen free radicals and the release of inflammatory cytokines. Its mechanism may be inhibition variety of inflammatory factors ,reducing pulmonary microcirculation permeability and decrea

关 键 词：VALI HO-1 炎性细胞因子 氧自由基 

分 类 号：R563.8[医药卫生—呼吸系统]