Hydrogen Sulfide Alleviates Lipopolysaccharide-Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF-κB Signaling Pathways

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-κB) 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-κB signaling pathways. Novel slow-releasing H(2)S donors can be designed and applied for the treatment of diaphragm dysfunction.