title: Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats.
abstract: Myocardial fibrosis is the predominant pathological characteristic of diabetic myocardial damage. Previous studies have indicated that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, there is little research investigating the effect of H2S on myocardial fibrosis in diabetes. The present study aimed to investigate the effects of H2S on the progression of myocardial fibrosis induced by diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Sodium hydrosulfide (NaHS) was used as an exogenous donor of H2S. After 8 weeks, expression levels of cystathionine-γ-lyase were determined by western blot analysis and morphological changes in the myocardium were assessed by hematoxylin and eosin staining and Masson staining. The hydroxyproline content and fibrosis markers were determined by a basic hydrolysis method and western blot analysis, respectively. Autophagosomes were observed under transmission electron microscopy. Expression levels of autophagy-associated proteins and their upstream signaling molecules were also evaluated by western blotting. The results of the current study indicated that diabetes induced marked myocardial fibrosis, enhanced myocardial autophagy and suppressed the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase (PI3K/AKT1) signaling pathway. By contrast, following treatment with NaHS, myocardial fibrosis was ameliorated, myocardial autophagy was decreased and the PI3K/AKT1 pathway suppression was reversed. The results of the present study demonstrated that the protective effect of H2S against diabetes-induced myocardial fibrosis may be associated with the attenuation of autophagy via the upregulation of the PI3K/AKT1 signaling pathway.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ou
authors.initials: O
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000473:pathology*; D005355:Fibrosis; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020782:Matrix Metalloproteinases; D003542:Cystathionine gamma-Lyase; D006909:Hydroxyproline; D006862:Hydrogen Sulfide