title: [The function of nuclear factor-erythroid 2-related factor 2 and its association with I-kappa B kinases alpha/beta in a rat model of chronic obstructive pulmonary disease.].
abstract: 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-Delta2, 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, IKKalpha/beta and NF-kappaB 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
  FEV(0.3)/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 H2Oxml(-1)xs(-1) were significantly higher than that of the normal control group (0.34 +/- 0.06) cm H2Oxml(-1)xs(-1). The above measurements of the drug intervention group [(74.5 +/- 3.9)%, (0.30 +/- 0.04) ml/cm H2O, (1.90 +/- 0.24) U/ml, (39.7 +/- 1.9) U/ml and (0.43 +/- 0.05) cm H2Oxml(-1)xs(-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, IKKalpha/beta and NF-kappaB p65 were increased significantly in the COPD models (3.23 +/- 0.31, 3.80 +/- 0.16 and 3.85 +/- 0.18, respectively), as compared with the control group (0.91 +/- 0.45, 1.17 +/- 0.42 and 1.30 +/- 0.34, respectively). The expression of IKKalpha/beta (2.10 +/- 0.46) and NF-kappaB p65 (2.53 +/- 0.36) in the lungs of the intervention group was between the COPD group and the control group, but the expression of Nrf2 (3.78 +/- 0.22) increased as compared to the COPD group. The results of RT-PCR showed that, the mRNA IOD value of Nrf2, IKKbeta and NF-kappaB p65 increased significantly in the COPD group (0.61 +/- 0.08, 0.89 +/- 0.05 and 0.91 +/- 0.02, respectively), as compared with the control group (0.29 +/- 0.07, 0.30 +/- 0.07, 0.30 +/- 0.07, respectively), while the expression of IKKbeta (0.67 +/- 0.04) and NF-kappaB p65 (0.69 +/- 0.04) in the lungs of the drug intervention group were between the above two groups, and the expression of Nrf2 (0.90 +/- 0.05) increased as compared to the COPD group.
  
  
  CONCLUSIONS
  15d-PGJ2 was shown to have anti-oxidation and anti-inflammation effects in this COPD model, which may be related to the increase of Nrf2. Nrf2 inhibited the expression of NF-kappaB p65 possibly through the down-regulation of IKKbeta.
authors.affiliation: Respiratory Department of Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Bai-Ling
authors.initials: BL
authors.lastname: Luo
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Chen
mesh_terms: D000818:Animals; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D008168:Lung; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive; D051381:Rats
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D051550:I-kappa B Kinase