核因子相关因子-2在慢性阻塞性肺疾病大鼠模型中的作用及其与I—κB激酶的关系  

The function of nuclear factor-erythroid 2-related factor 2 and its association with I-kappa B kinases α/β in a rat model of chronic obstructive pulmonary disease

作　　者：李秀英[1] 罗百灵[1] 陈红梅[1] 

机构地区：[1]中南大学湘雅医院呼吸内科,长沙410008

出　　处：《中华结核和呼吸杂志》2009年第12期935-939,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：【摘要】目的探讨核因子相关因子-2（Nrf2）在COPD发病中的作用及与核因子-κB和I—κB激酶（IKKs）之间的关系。方法将大鼠按照完全随机方法分为对照组、模型组和干预组，每组12只，检测大鼠的肺功能和抗氧化能力。免疫组织化学SABC法和逆转录PCR法检测Nrf2、核因子-κB p65和IKKoL／[3的蛋白水平及mRNA表达。统计学方法采用单因素方差分析，组间两两比较采用LSD-t检验。结果模型组大鼠FEV0.3／FVC为（58．8±2．6）％，动态肺顺应性为（0．14±0．02）ml／cm H2O（1cm H2O=0．098kPa），总抗氧化能力为（0．20±0．03）U／ml，SOD抗氧化能力为（19．6±2．4）U／ml，均明显低于对照组[（86．3±2．5）％、（0．38±0．02）ml／cm H2O、（3．16±0．31）U／ml及（56．1±2．2）U／ml]；模型组大鼠的气道阻力为（0．69±0．17）cm H2O·ml^-1·s^-1，明显高于对照组的（0．34±0．06）cm H2O·ml^-1·s^-1；干预组介于两组之间。模型组大鼠Nrf2、IKKα／β和核因子-κB p65的阳性系数依次为3．23±0．31、3．80±0．16和3．85±0．18，明显高于对照组的0．91±0．45、1．17±0．42和1．30±0．34，干预组IKKα／β和核因子-κB p65的阳性系数（2．10±0．46和2．53±0．36）介于两者之间，而Nrf2的阳性系数（3．78±0．22）明显高于模型组。模型组大鼠Nrf2、IKKβ和核因子-κB p65的mRNA表达分别为0．61±0．08、0．89±0．05和0．91±0．02，明显高于对照组的0．29±0．07、0．30±0．07和0．30±0．07，干预组IKKβ和核因子-κB p65的mRNA表达（0．67±0．04和0．69±0．04）介于两者之间，而Nrf2的mRNA表达（0．90±0．05）明显高于模型组。结论15d—PGJ2在COPD模型中有抗氧化应激和抗炎症作用，这可能与Nrf2增加有关。Nrf2可能通过抑制IKKβ表达从而抑制核因子-κB p65的表达水平。Objective To study the expression of nuclear factor-erythroid 2-related factor 2 （Nrf2） in the bronchial and lung tissues of chronic obstructive pulmonary disease （ COPD ） rat models and its association with I-kappa B kinases （IKKs）. Methods Rat COPD models were established by intratracheal instillation of lipopolysaccharide （LPS） twice and exposure to cigarette smoke daily. The drug intervention group received 15-deoxy-△2,14-prostaglandin J2 （15d-PGJ2） 0. 3 mg/kg twice via tail venous injection. Spirometry was conducted and the pathological changes were observed. Antioxidation activities were measured and the expressions of Nrf2, IKKα/β and NF-κB p65 were detected by immunohistochemistry and RT-PCR. The differences among groups were calculated by one-way ANOVA, and comparison between groups was made by LSD-t test. Results FEV0.3/FVC, Cdyn values and antioxidation capacity including total anti-oxidation competence and superoxidase dismutase in the COPD group [ （58.8 ±2.6）%, （0. 14± 0. 02） ml/cm H2O（ 1 cm H2O = 0. 098 kPa）, （0. 20 ± 0. 03 ） U/ml and （ 19. 6 ± 2. 4） U/ml, respectively ] were significantly lower than those in the normal control group [ （ 86. 3 ±2. 5 ） %, （ 0. 38 ±0. 02 ） ml/ cm H2O, （3. 16 ±0.31 ） U/ml and （56. 1 ±2.2） U/ml, respectively] . RI values （0.69 ±0. 17） cm H2O ·ml^-1·s^-1 were significantly higher than that of the normal control group （0. 34 ±0. 06）cm H2O ·ml^-1·s^-1. The above measurements of the drug intervention group [ （ 74. 5 ±3.9 ） %, （ 0.30 ±0.04 ） ml/cmH2O, （1.90 ±0.24）U/ml, （39.7 ±1.9）U/ml and （0.43±0.05）cm H2O ·ml^-1·s^-1, respectively] were between the COPD and the control groups, with airflow limitation and pulmonary ventilation improved significantly. Immunohistochemistry showed that, the positive coefficient of Nrf2, IKKα/β and NF-κB p65 were increased significantly in the COPD models （3.23 ±0. 31, 3.80 ±0. 16 and 3.85 ±0. 18, respectively） , as compared wi

关 键 词：肺疾病 慢性阻塞性 I-κB激酶 NF—κB 

分 类 号：R563.9[医药卫生—呼吸系统]