[Shenqi Tiaoshen Formula alleviates airway inflammation in rats with chronic obstructive pulmonary disease and kidney qi deficiency syndrome by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway].

Abstract

Objective: To investigate the effects of Shenqi Tiaoshen Formula (SQTSF) for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease (COPD) and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.

Methods: Forty-eight SD rats were randomly divided into control group, model group, low-, medium-, and high-dose SQTSF groups, and aminophylline (APL) group. In all but the control group, rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline, SQTSF or APL via daily gavage as indicated (starting from day 30). The rats were observed for changes in body weight, grip strength, lung function, lung pathology, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), oxidative stress levels, iron ion metabolism, cellular and mitochondrial ultrastructural changes in the lung tissue, and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.

Results: The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight, grip strength, and lung function parameters. Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial, perivascular, and alveolar inflammation and alveolar destruction, significantly increased IL-1β, TNF-α, IL-6, and IL-13 levels in BALF, and elevated pulmonary oxidative stress levels and Fe²⁺ and total iron ion concentrations. The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2, GPX4, and SLC7A11 and increased ACSL4 expressions in the lung tissue. Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.

Conclusion: SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.