Hydrogen Sulfide Alleviates Lipopolysaccharide‐Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF‐<i>κ</i>B Signaling Pathways

Abstract

Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H 2 S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H 2 S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H 2 S was decreased in lipopolysaccharide‐ (LPS‐) treated L6 cells. Treatment with H 2 S increased the proliferation and viability of LPS‐treated L6 cells. We found that H 2 S decreased reactive oxygen species‐ (ROS‐) induced apoptosis through the mitogen‐activated protein kinase (MAPK) signaling pathway in LPS‐treated L6 cells. Administration of H 2 S alleviated LPS‐induced inflammation by mediating the toll‐like receptor‐4 (TLR‐4)/nuclear factor‐kappa B (NF‐ κ B) signaling pathway in L6 cells. Furthermore, H 2 S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H 2 S ameliorates LPS‐induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF‐ κ B signaling pathways. Novel slow‐releasing H 2 S donors can be designed and applied for the treatment of diaphragm dysfunction.