The Protective Role of Hydrogen Sulfide and Its Impact on Gene Expression Profiling in Rat Model of COPD.

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, which is usually caused by exposure to noxious particles or gases. Hydrogen sulfide (H₂S), as an endogenous gasotransmitter, is involved in the pathogenesis of COPD, but its role in COPD is little known. To investigate the role of H₂S in COPD, a rat model of COPD was established by cigarette smoking (CS) and intratracheal instillation of lipopolysaccharide (LPS). Rats were randomly divided into 4 groups: control, CS + LPS, CS + LPS + sodium hydrosulfide (NaHS, H₂S donor), and CS + LPS + propargylglycine (PPG, inhibitor of cystathionine-γ-lyase, and CTH). Lung function in vivo, histology analysis of lung sections, malondialdehyde (MDA) concentration, CTH protein, total superoxide dismutase (T-SOD), and catalase (CAT) activity in lung tissues were assessed. Gene expression profiling of lung was assessed by microarray analysis. The results showed that rats in the CS + LPS group had lower body weight and lung function but higher lung pathological scores, MDA concentration, CTH protein, T-SOD, and CAT activity compared with the control. Compared with CS + LPS group, NaHS treatment decreased lung pathological scores and MDA concentration, while PPG treatment decreased body weight of rats and T-SOD activity, and no significant differences were detected in pathological scores by PPG treatment. Microarray analysis identified multiple differentially expressed genes, and some genes regulated by H₂S were involved in oxidative stress, apoptosis, and inflammation pathways. It indicates that H₂S may play a protective role in COPD via antioxidative stress and antiapoptosis pathway.