Hydrogen sulfide prevents diaphragm weakness in cecal ligation puncture-induced sepsis by preservation of mitochondrial function

• Published in: American journal of translational research Vol. 9; no. 7; pp. 3270 - 3281
• Main Authors: Zhang, Hai-Xia, Du, Jun-Ming, Ding, Zhong-Nuo, Zhu, Xiao-Yan, Jiang, Lai, Liu, Yu-Jian
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2017
• Subjects: Original; Hydrogen sulfide; diaphragm weakness; mitochondria; sepsis
• ISSN: 1943-8141; 1943-8141

Mitochondrial dysfunction plays an important role in the pathogenesis of diaphragm weakness during sepsis. Recently, hydrogen sulfide (H S), a gaseous transmitter endogenously generated by cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), is found to improve mitochondrial function. The present study aimed to examine whether H S synthases are expressed in the diaphragm, and investigated the effect of H S donor in sepsis-induced diaphragm weakness and its relationship with mitochondrial function. Immunohistochemical staining of the rat diaphragm revealed that positive immunoreactivity for CBS, CSE as well as 3-MST was predominately localized to muscle cells. Using a cecal ligation and puncture (CLP)-induced sepsis model, it was found that CBS and CSE, but not 3-MST, was significantly down-regulated in the diaphragm at 24 h post-CLP compared with sham group. To determine the effect of H S on sepsis-induced diaphragm weakness, H S donor NaHS was intraperitoneally administered 30 min after CLP operation. NaHS at a dose of 50 μmol/kg significantly decreased the mortality in septic rats. CLP markedly reduced diaphragm-specific force generation (force/cross-sectional area and maximal titanic force), which was improved by NaHS treatment. In addition, CLP caused mitochondrial damage in the diaphragm tissues as evidenced by increased mitochondrial superoxide production, decreased mitochondrial membrane potential and ATP production, as well as mitochondrial ultrastructural abnormalities, which was also attenuated by NaHS treatment. These findings indicate that H S donor may prevent sepsis-induced diaphragm weakness by preservation of mitochondrial function, suggesting that modulation of H S levels may be considered as a potential therapeutic approach for diaphragm dysfunction during sepsis.