Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
Sci Rep. 2017 Sep 20;7(1):12026. doi: 10.1038/s41598-017-12285-8.
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 PaO/FiO 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.
败血症是一种危及生命的医疗状况。从红景天中分离出来的红景天苷具有抗氧化和抗炎特性。红景天苷对败血症引起的急性肺损伤的作用和机制仍有待阐明。在这里，我们研究了红景天苷对败血症小鼠模型的作用和机制，并探讨了红景天苷上调 SIRT1 的作用。红景天苷抑制了细菌脂多糖（LPS）处理的巨噬细胞和小鼠中的炎症反应和高迁移率族蛋白 B1（HMGB1）的产生。红景天苷还可以逆转 LPS 处理的巨噬细胞和小鼠中 SIRT1 蛋白表达的降低。红景天苷还减轻了败血症引起的肺水肿、脂质过氧化和组织病理学变化以及死亡率，并改善了盲肠结扎和穿刺（CLP）诱导的败血症小鼠的肺 PaO/FiO 比值。红景天苷显著降低了 CLP 败血症小鼠的血清 TNF-α、IL-6、NO 和 HMGB1 的产生、肺诱导型一氧化氮合酶（iNOS）和磷酸化 NF-κB-p65 蛋白的表达以及肺 HMGB1 核转位。此外，败血症降低了 CLP 败血症小鼠肺部的 SIRT1 蛋白表达。红景天苷显著上调了 SIRT1 的表达，并抑制了 CLP 败血症小鼠肺部的炎症反应。这些结果表明，红景天苷可以预防败血症引起的急性肺损伤和死亡率，这可能是通过 SIRT1 介导的抑制 NF-κB 激活和 HMGB1 核质转运。
