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目的:观察脑死亡引发的肺脏损伤性改变,探讨吸入氢气的脑死亡大鼠的肺相关功能的保护机制。方法:郑州大学基础医学院实验动物中心提供的成年、雄性Wistar大鼠21只,体重200~300 g,将其随机分成3组:脑死亡组(BD组,n n=7),用缓慢颅内加压的相关研究方法对其建立脑死亡的模型,模型成功后吸入氮气、氧气混合的气体(50%On 2+50%Nn 2)90 min;假手术组(S组,n n=7),除了不给予硬脑膜外的颅内加压外,其他处理同脑死亡组;脑死亡吸入氢气组(BDHn 2组,n n=7),脑死亡模型制备成功后吸入氮气、氧气、氢气混合的气体(2%Hn 2+50%On 2+48%Nn 2)90 min。大鼠脑死亡成功后(0、30、60、90 min)测定动脉血气值,收集对应的动脉血和肺组织,检测其血浆中白细胞介素(IL)-8、肿瘤坏死因子-α(TNF-α)的浓度,测定其肺组织中超氧化物歧化酶(SOD)的活性、丙二醛(MDA)的浓度、髓过氧化物酶(MPO)的活性、细胞间黏附分子-1(ICAM-1)和半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3蛋白的表达,苏木精-伊红(HE)行肺损伤程度观察,计算肺组织损伤评分(LIS评分)。血气分析组间比采用重复测量设计的方差分析,其他指标组间比采用单因素方差分析。n 结果:与S组比较,BD、BDHn 2组氧合指数(PaOn 2/FiOn 2)值(301.3±31.0、352.9±29.0)、肺组织中SOD活性[(10.64±1.25)、(12.8±2.17) U/mg蛋白]、ICAM-1和Caspase-3蛋白的表达降低(4.76±0.89、2.89±0.65、5.92±1.03、3.01±0.94),差异有统计学意义(n F=27.440、4.983、3.732、4.237,n P<0.05),BD、BDHn 2组肺组织中MDA含量[(7.52±1.34)、(5.99±0.64) nmol/mg蛋白]、血浆IL-8[(538±140)、(423±64) pg/ml]及TNF-α的浓度[(796±213)、(569±158) pg/ml]、LIS评分升高[(9.28±2.25)、(4.70±2.10)分],差异有统计学意义(n F=6.053、10.079、9.759、4.021,n P<0.05);与BD组比较,BDHn 2组PaOn 2/FiOn 2、肺组织SOD活性、ICAM-1和Caspase-3蛋白的表达升高,差异有统计学意义(n F=27.440、4.983、3.732、4.237,n P<0.05),肺组织中MDA含量、血浆IL-8及TNF-α的浓度、LIS评分降低,差异有统计学意义(n F=6.053、10.079、9.759、4.021,n P<0.05)。n 结论:脑死亡使大鼠肺脏发生损伤性的改变,而吸入2%氢气能够减轻脑死亡所诱发的肺脏损伤。“,”Objective:To investigate the changes in lung function of brain death (BD)-induced lung injury and to explore the protection and mechanism of inhalation of 2% hydrogen for BD-induced lung injury.Methods:Twenty-one pathogen free adult Wistar rats were randomly assigned into three groups: brain dead group (BD group, n n=7), Sham group (S group, n n=7) and hydrogen protection group (BDHn 2 group, n n=7). Brain-death models were established in BD group and BDHn 2 group. Rats inhale mixed gas (hydrogen gas 2%, oxygen gas 50%, nitrogen gas 48%) in BDHn 2 group while rats inhale mixed gas (oxygen gas 50%, nitrogen gas 50%) in BD and S group. The arterial blood gas analysis was performed at 0, 30, 60, 90 min after conformation of brain-death. The plasma concentrations of interleukin (IL)-8 and tumor necrosis factor-α (TNF-α) and the activity of superoxide dismutase (SOD), malonaldehyde (MDA) and myeloperoxidase (MPO) in the lungs were measured. The lung injury score (LIS) was recorded. The protein expression of intercellular adhesion molecule-1 (ICAM-1) and cysteinyl aspartate-specific protease (Caspase)-3 in lung tissue were measured by immunohistochemistry.n Results:Compared with S group, the values of partial pressure of blood oxygen (PaOn 2)/concentration of inhaled oxygen (FiOn 2, 301.3±31.0, 352.9±29.0), SOD activity [(10.64±1.25), (12.8±2.17) U/mg·prot], the expression of ICAM-1 and Caspase-3 protein (4.76±0.89, 2.89±0.65, 5.92±1.03, 3.01±0.94) were decreased in BD and BDHn 2 group, and the differences were statistically significant (n F=27.440, 4.983, 3.732, 4.237, n P<0.05); MDA content [(7.52±1.34), (5.99±0.64) nmol/mg·prot], IL-8 [(538±140), (423±64) pg/ml], TNF-α [(796±213), (569±158) pg/ml] and LIS score (9.28±2.25, 4.70±2.10) were increased in BD and BDHn 2 group, and the differences were statistically significant (n F=6.053, 10.079, 9.759, 4.021, n P<0.05). Compared with the BD group, the values of PaOn 2/FiOn 2, SOD activity, the expression of ICAM-1 and Caspase-3 protein were increased in the BDHn 2 group, and the differences were statistically significant (n F=27.440, 4.983, 3.732, 4.237, n P<0.05); MDA content, the concentrations of IL-8 and TNF-α and LIS score were decreased, and the differences were statistically significant (n F=6.053, 10.079, 9.759, 4.021, n P<0.05).n Conclusion:Inhalation of 2% hydrogen can ameliorate BD-induced lung injury in rats.