Abstract
It has been revealed that widespread vascular endothelial dysfunction occurs in septic shock, ultimately resulting in multiple organ failure. The mitochondrial deacetylase sirtuin 3 (SIRT3) is essential in the regulation of metabolism, anti-inflammation, and anti-oxidation. The purpose of this study is to investigate whether SIRT3 is associated with the pathological progression of endothelial dysfunction in sepsis. Septic shock model was induced by cecal ligation and puncture (CLP) surgery on wild-type C57BL/6 mice. We activated and inhibited the function of SIRT3 with honokiol (HKL) and 3-TYP, respectively, and then biochemical, inflammatory, and endothelial function parameters of vascular tissue and survival were determined after CLP. CLP significantly activated NF-κB and NLRP3 pathways and decreased survival rate, endothelium-dependent relaxation function, and expression of Ser1177 phosphorylation of endothelial nitric oxide synthase (p-eNOS). The activation of SIRT3 significantly attenuated the increases of NF-κB and NLRP3 pathways and the declines of p-eNOS, endothelium-dependent relaxation function, and survival rate in septic mice. However, it presented exactly opposite results if SIRT3 was suppressed. We suggested that SIRT3 had a critical protective effect against vascular inflammation and endothelial dysfunction in early sepsis. Our data support a potential therapeutic target in vascular dysfunction and septic shock.