血红素加氧酶-l调节哮喘豚鼠的氧化-抗氧化失衡

Heme oxygenase-1 regulates oxidant and antioxidant imbalance in guinea pigs with asthma

目的探讨血红素加氧酶-1（heme oxygenase-1，HO-1）在哮喘氧化-抗氧化反应中的作用及机制。方法30只豚鼠完全随机分为3组，每组10只。哮喘组：参照Huston法，用卵蛋白（ovalbumin，OVA）建立哮喘豚鼠模型。地塞米松组：应用地塞米松防治哮喘豚鼠模型。正常对照组：用n9％生理盐水代替OVA致敏豚鼠，诱发同哮喘组。各组豚鼠应用分光光度法分别检测肺组织HO-1活性、血清及肺组织脂质过氧化物丙二醛（MDA）含量、血清抗氧化物胆红素含量，观察肺组织病理变化及HO．1蛋白表达。结果哮喘组肺组织HO-1活性增加[生成胆红素量为（901．12±321．53）pmol／（mgprotein·h）]、血清和肺组织MDA增加[血清MDA为（12．25±2．49）mmol／ml，肺组织MDA为（69．38±7．49）nmol／mgprotein]、血清胆红素减少[（0．54±0．23）pmol／L]，与正常对照组和地塞米松组比较差异均有统计学意义（P〈0．01）。哮喘组肺组织HO-l蛋白表达为3-4级。地塞米松组前3项指标较哮喘组显著下降（P〈o．01），而血清胆红素水平较哮喘组显著上升（P〈0．01），而与正常对照组比较差异无统计学意义（P〉D．05）；肺组织HO-1蛋白表达为1～2级。结论哮喘发作时体内HO-1蛋白表达和活性增加，用以代偿胆红素的减少，调节哮喘的氧化-抗氧化失衡，保护机体防御氧化应激损伤，减轻哮喘过敏症状或气道高反应性。

Objective To explor the antioxidant effects of heme oxygenase-1 （ HO-1 ） for asthma and its mechanism. Methods Thirty two months old healthy male guinea pigs were randomly assigned to 3 groups, all of them were feed under the same management condition. Asthmatic group, refering to Huston＇s research results, were sensitized by exposure to aerosolized ovalbumin（OVA） in order to build the guinea pig motile of asthma. Dexamethasone group （ DG）, were also sensitized by exposur to aerosolized ovalbumin as well as the asthraatic group had done and then treated with dexamethasone. Normal control group （NCG） ： were treated with 0. 9% sterile sodium chloride. All the tested animals were measured the activity of lung HO-1 ,levels of malondialdehyde （MDA） in the lung tissue or serum and bilirubin in the serum by spectro photometry. And the pathology and expression of HO-lprotein in the lung tissue were observed. Results In the OVA induced asthmatic group ,the HO-1 activity and level of MDA in lung tissue or serum were markedly increased compared with the groups of NCG and DG （ P 〈0. 01 ） and the expression of lung HO-1 protein was as 3-4 grade. While level of b＇llirubin was markedly reduced compared with NCG and DG. For example,in asthmatic group,the activity of lung HO-1 was,the level of bilirubin formed,（901.12 ＋321.53） pmol/（mg protein.h）. The level of MDA in senma was（ 12. 25 ＋2. 49） mmoL/ml. The level of lung MDA was（69. 38 ＋ 7. 49） nmol/mg protein,and the level of bilimbin in serum was （0. 54 ＋_0.23 ） pmol/L. In DG,the data of HO-1 and MDA as described above were markedly reduced compared with the OVA induced asthmatic group（P 〈0. 01 ） ,and lung pro- tein expression was 1-2 grade,while the level of bilirubin in the serum was increased（P 〈 0. 01 ）. But,all datas of DG had no significant difference compared with NCG （ P 〉 0. 05 ）. Conclusion The guinea pigs＇ in vivo lipid peroxide level increases and the level of bilirubin, an antioxidant, markedly decrease during asthma attacks, which induce the imbalance of oxidant and antioxidant. Content level and activity of HO-1 protein can in crease in asthma body in order to compensate the reduce of bilirubin level, regulate the imbalance of oxidant and antioxidant, protect lung tissues from oxidizing reaction damage and relieve allergy or asthma symptoms.