Effect Of PM2.5 On The Level Of Nuclear Factor Erythroid-2 Related Factor 2 In Chronic Obstructive Pulmonary Disease Mice And Its Relationship With Oxidative Stress

Objective To explore the level of nuclear factor erythroid-2 related factor 2(Nrf2) in chronic obstructive pulmonary disease(COPD) mice and its relationship with oxidative stress after fine particulate matter with an aerodynamic diameter less than 2.5 μm(PM2.5) intervened..Methods 40 male mice were randomly divided into a normol control group, a normol PM2.5 group, a COPD control group and a COPD PM2.5 group. The number of mice in each group was 10. COPD mice were established using exposure of cigarette smoking. Mice in normal PM2.5 group and COPD PM2.5 group were intervened with intratracheal instillation of PM2.5suspension. Mice in control group were instilled with an equal volume of salt solution. Mice pulmonary function were measured by mice noninvasive body plethysmograph and lung histopathology was observed. The mRNA and protein expression of Nrf2 was measured with real-time PCR and Westernblot. The contents of total antioxidant capacity(TAC), glutathione peroxidase(GSH-Px) and malondialdehyde(MDA) were measured with colorimetric method.Results 1. PIF, PEF and EF50% of COPD control group(5.64±0.24),(3.48±0.33) and(3.15±0.33)ml/s were significantly lower than normol control group(9.94±0.42),(6.70±0.45) and(4.92±0.45)ml/s( all P < 0.01). The alveolar wall is thinned and expanded. Part of alveolar space emphysema is fused into bullae rupture in COPD mice. The result of pathology is in accord with COPD characteristic performance.2. The mRNA and protein of Nrf2 were higher in COPD control group( 4.93 ± 0.63),( 1.20± 0.09) than normol control group 1.00,( 0.92 ± 0.08)( all P < 0.01). After PM 2.5 intervened,The mRNA and protein of Nrf2 in normol PM2.5 group( 4.46 ± 0.42) and( 1.23 ± 0.07) were higher than normol control group( all P < 0.01). The above parameters in COPD PM2.5 group( 6.41 ± 0.35) and( 1.43 ± 0.10) were increased as compared to in COPD control group( all P <0.01). The levels of Nrf2 mRNA and protein in COPD PM2.5 group were higher than normol PM2.5 group( all P< 0.01).3. The levels of TAC and GSH-Px were lower in COPD control group( 3.29 ± 0.31) and( 9.82 ± 0.69) U/mgprot as compared to normol control group( 5.09 ± 0.39) and( 13.43 ± 0.49)U/mgprot( all P < 0.01). The level of MDA was higher in COPD control group( 4.54 ± 0.33)nmol/mgprot than normol control group( 2.94 ± 0.37) nmol/mgprot( all P < 0.01).. After PM 2.5intervened, the levels of TAC and GSH-Px in normol PM2.5 group( 2.85 ± 0.35) and( 9.87 ±0.70) U/mgprot were lower than normol control group. Similarly, these parameters in COPD PM2.5 group( 1.80 ± 0.32) and( 7.03 ± 0.56) U/mgprot were also decreased as compared to COPD control group( all P < 0.01). However, the level of MDA in normol PM2.5 group( 4.76 ±0.48) nmol/mgprot was higher than normol control group( all P < 0.01). The above parameter in COPD PM2.5 group( 6.24 ± 0.37) nmol/mgprot was increased as compared to in COPD control group( all P < 0.01). The levels of TAC and GSH-Px in COPD PM2.5 group were lower than those in normol PM2.5 group( all P< 0.01). However, the level of MDA in COPD PM2.5 group was higher than normol PM2.5 group( all P< 0.01).4.(1) Negative correlations were existed between Nrf2 mRNA and TAC, GSH-Px( r=-0.84P<0.01, r=-0.75 P<0.05), while positive correlations were existed between Nrf2 mRNA and MDA( r=0.79 P<0.01) in normol control group. Negative correlations were existed between Nrf2 protein and TAC, GSH-Px( r=-0.87 P<0.01, r=-0.72 P<0.05), while positive correlations were existed between Nrf2 protein and MDA( r=0.79 P<0.01) in normol control group.(2) Negative correlations were existed between Nrf2 mRNA and TAC, GSH-Px( r=-0.89P<0.01, r=-0.74 P<0.05), while positive correlations were existed between Nrf2 mRNA and MDA( r=0.85 P<0.01) in COPD control group. Negative correlations were existed between Nrf2 protein and TAC, GSH-Px( r=-0.83 P<0.01, r=-0.74 P<0.05), while positive correlations were existed between Nrf2 protein and MDA( r=0.73 P<0.05) in COPD control group.(3) Negative correlations were existed between Nrf2 mRNA and TAC, GSH-Px( r=-0.78P<0.01, r=-0.85 P<0.01), while positive correlations were existed between Nrf2 mRNA and MDA( r=0.88 P<0.01) in normol PM2.5 group. Negative correlations were existed between Nrf2 protein and TAC, GSH-Px( r=-0.84 P<0.01, r=-0.86 P<0.01), while positive correlations were existed between Nrf2 protein and MDA( r=0.86 P<0.01) in normol PM2.5 group.(4) Negative correlations were existed between Nrf2 mRNA and TAC, GSH-Px( r=-0.82P<0.01, r=-0.75 P<0.05), while positive correlations were existed between Nrf2 mRNA and MDA( r=0.74 P<0.05) in COPD PM2.5 group. Negative correlations were existed between Nrf2 protein and TAC, GSH-Px( r=-0.86 P<0.01, r=-0.90 P<0.01), while positive correlations were existed between Nrf2 protein and MDA( r=0.74 P<0.05) in COPD PM2.5 group.Conclusion 1.Exposed to cigarette smoke could be successfully established the model of COPD mice. 2. Oxidative stress was exsited in COPD. The increased levels of oxidative stress could promote Nrf2 expression in COPD. 3. PM2.5 could increase Nrf2 expression and aggravateoxidative stress in lung tissue. 4. The increased Nrf2 expression induced by PM2.5 was closely associated with oxidative stress in lung tissue.