Abstract
Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.
Highlights
Sepsis is a life-threatening medical condition characterised by dysregulated inflammation, dysfunctional blood coagulation, and multiple organ injuries[1]
LPS treatment markedly induced the inducible NO synthase (iNOS) protein expression (Fig. 1C) and nuclear factor (NF)-κB p65 phosphorylation (Fig. 1D), but decreased the SIRT1 protein expression (Fig. 1E) in macrophages, which could be significantly reversed by salidroside in a dose-dependent manner
We used the LPS-induced systemic inflammation mouse model or cecal ligation and puncture (CLP)-induced murine sepsis model to investigate the therapeutic role of salidroside in sepsis-induced acute lung injury
Summary
Sepsis is a life-threatening medical condition characterised by dysregulated inflammation, dysfunctional blood coagulation, and multiple organ injuries[1]. Severe inflammation can be deleterious, resulting in multiple organ dysfunction, including acute lung injury. Patients with sepsis-induced acute lung injury had greater illness severity and organ dysfunction[6]. Bacteria lipopolysaccharide (LPS) can cause HMGB1 acetylation, resulting in the localization of the protein to the cytosol[7]. Salidroside protected septic rats from acute lung injury by upregulating peroxisome proliferator-activated receptor γ expression and attenuating LPS-activated NF-κB signaling[17]. We hypothesized that SIRT1 signaling pathway might be involved in the therapeutic effect of salidroside on sepsis-induced acute lung injury. We used a bacterial lipopolysaccharide (LPS)-induced systemic inflammation mouse model and a cecal ligation and puncture (CLP)-induced sepsis mouse model to investigate the protective effects of salidroside and explore the possible underlying action mechanisms
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