Objective To explore the possible mechanism of lung injury caused by high temperature and PM2.5 in chronic obstructive pulmonary disease (COPD) rats.
Methods Eighty-four healthy seven-week-old SPF male Wistar rats were randomly divided into control group and COPD model groups. A COPD rat model was established by cigarette smoke exposure and intratracheal instillation of lipopolysaccharide. The rats were instilled with PM2.5 (0, 3.2, and 12.8mg/mL) separately and then exposed to high temperature at 40℃ for 8h, once a day for three consecutive days; 20℃ was selected as the normal control temperature. Lung function indicators peak inspiratory flow (PIF) and peak expiratory flow (PEF) were measured 24 h after the last exposure. Lung tissue samples were collected for pathologic analysis by HE staining. The levels of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and malonyldialdehyde (MDA) in lung homogenate of COPD rats were detected by corresponding test kits. The expression levels of 8-hydroxydeoxyguanosine (8-OHdG) and heme oxygenase (HO-1) were determined by streptomycin anti-biotin-peroxidase and Western blot respectively. Factorial analysis was used to analyze the effects of temperature, PM2.5, and COPD on lung function, and also the effects of temperature and PM2.5 on oxidative stress indicators.
Results Under high temperature stimulation, the PIF and PEF of the control and COPD rats treated with different PM2.5 doses were lower than the rats treated with corresponding exposure dose at normal temperature (Ps < 0.05); high temperature, PM2.5, and COPD had interactions on PIF (F=7.585, P < 0.05). The injury in lung tissues of the COPD rats was obvious, especially under high temperature and PM2.5 exposure, which was more obvious than that in the control group. The content of iNOS in lung tissues of the COPD group under high temperature was higher than that of the COPD group under normal temperature treated with various doses of PM2.5 (Ps < 0.05). There was no interaction between high temperature and PM2.5 on MDA (F=1.779, P=0.183), iNOS (F=0.128, P=0.880), and SOD (F=1.792, P=0.175). In addition, the expression of 8-OHdG protein in lung tissues of the COPD group under high temperature was higher than that of the COPD group under normal temperature treated with 0 and 3.2mg/mL PM2.5 (P < 0.05); the expression of HO-1 protein in the COPD rats under high temperature was lower than that in the rats under normal temperature at 0 and 12.8mg/mL PM2.5 (P < 0.05).
Conclusion COPD rats' lung function is more susceptible to PM2.5 under high temperature, and the imbalance of oxidative/antioxidant system may be the main mechanism of lung injury in COPD rats with high temperature and PM2.5 co-exposure.
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