Gu-Ben-Zhi-Ke-Zhong-Yao Alleviated PM2.5-Induced Lung Injury via HMGB1/NF-κB Axis

BACKGROUND: Inhalation of particles with a diameter of less than 2.5 μm (PM2.5) among air pollutants may cause lung damage. Gu-Ben-Zhi-Ke-Zhong-Yao (GBZK) is a traditional Chinese medicine prescription that has a beneficial effect on the treatment of chronic obstructive pulmonary disease (COPD). However, the effect of GBZK on PM2.5-induced lung injury remains to be elucidated. METHODS: We constructed a mice lung injury model through PM2.5 stimulation and simultaneously performed GBZK gavage treatment. After 4 weeks, the lung tissues of the mice were collected for pathological staining to analyze the degree of damage. The activities of myeloperoxidase (MPO), malondialdehyde (MDA), and oxidative stress-related factors (superoxide dismutase, SOD; glutathione peroxidase, GSH-Px) were detected by commercial kit in lung tissue. Furthermore, the number of neutrophils and related inflammatory factors (interleukin-1, IL-1β; tumor necrosis factor α, TNF-α; interleukin-6, IL-6) in bronchoalveolar lavage fluid (BALF) and serum were collected and tested to evaluate the effect of GBZK on inflammation. Masson staining was used to detect the level of lung fibrosis in mice. The activation of HMGB1 (high-mobility group protein 1) and NFκBp65 (nucleus factor kappa B) in lung tissue was evaluated by immunohistochemistry and western blot. RESULTS: The result revealed that PM2.5 induces lung damage, and GBZK gavage treatment could reduce the degree of injury in a concentration-dependent manner in mice. After GBZK treatment, the MPO activity, MDA content, and oxidative stress level in the lung tissues of mice decreased. And after GBZK treatment, the expression levels of inflammatory cytokines in BALF and blood were decreased. GBZK treatment also improved pulmonary fibrosis in mice. In addition, we also found that GBZK prevented the up-regulation of the HMGB1/NF-κB axis in the lungs of mice. CONCLUSION: These results indicated that GBZK might protect mice from PM2.5-induced lung injury by inhibiting the HMGB1/NFκB pathway, thus repressing inflammation and pulmonary fibrosis.