Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats.

Impact Statement: Diabetes mellitus is a group of chronic metabolic disorders, which causes serious damage to a variety of organs, such as the retina, heart, and skeletal muscle. The diaphragm is an important skeletal muscle involved in respiration in mammals. Fibrosis of the diaphragm muscle affects its contractility, which in turn impairs respiratory function. Accumulating evidence suggests that exogenous hydrogen sulfide (H ₂ S) exhibits anti-fibrotic activity in diabetes mellitus, but whether and how H ₂ S exerts this anti-fibrotic effect in the diabetic diaphragm remains unclear. The current work for the first time reveals that exogenous H ₂ S attenuates hyperglycemia-induced fibrosis of the diaphragm muscle and strengthens diaphragmatic biomechanical properties in diabetes mellitus, and the mechanism may involve the alleviation of collagen deposition by suppression of the nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-mediated inflammatory reaction. Therefore, H ₂ S supplementation could be used as an efficient targeted therapy against the NLRP3 inflammasome in the diabetic diaphragm.