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, $\text{CS}+\text{LPS}$ , $\text{CS}+\text{LPS}+\text{sodium}\text{hydrosulfide}$ (NaHS, H2S donor), and $\text{CS}+\text{LPS}+\text{propargylglycine}$ (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 $\text{CS}+\text{LPS}$ 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 $\text{CS}+\text{LPS}$ 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.