Sepsis is a life-threatening condition. Polydatin (PD), a small natural compound from Polygonum cuspidatum, possesses antioxidant and anti-inflammatory properties. However, the protective mechanism of PD on sepsis-induced acute myocardial damage is still unclear. The aim of this study was to investigate the effect and mechanism of action of PD on lipopolysaccharide (LPS)-induced H9c2 cells and in a rat model of sepsis, and explored the role of PD-upregulated sirtuin (SIRT)6. LPS-induced H9c2 cells were used to simulate sepsis. Cecal ligation and puncture (CLP)-induced sepsis in rats were used to verify the protective effect of PD. ELISA, western blotting, immunofluorescence, immunohistochemistry, and flow cytometry were used to study the protective mechanism of PD against septic myocardial injury. PD pretreatment suppressed LPS-induced H9c2 cell apoptosis by promotion of SIRT6-mediated autophagy. Downregulation of SIRT6 or inhibition of autophagy reversed the protective effect of PD on LPS-induced apoptosis. PD pretreatment also suppressed LPS-induced inflammatory factor expression. CLP-induced sepsis in rats showed that PD pretreatment decreased CLP-induced myocardial apoptosis and serum tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 expression. 3-Methyladenine (autophagy inhibitor) pretreatment prevented the protective effect of PD on septic cardiomyopathy. SIRT6 expression was increased with PD treatment, which confirmed that PD attenuates septic cardiomyopathy by promotion of SIRT6-mediated autophagy. All these results indicate that PD has potential therapeutic effects that alleviate septic myocardial injury by promotion of SIRT6-mediated autophagy.

中文翻译：

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Polydatin通过促进SIRT6介导的自噬减轻了败血症性心肌损伤。

败血症是威胁生命的状况。虎杖（Polydatin）是虎杖中的一种天然小化合物，具有抗氧化和抗发炎的特性。然而，PD对败血症诱导的急性心肌损伤的保护机制仍不清楚。这项研究的目的是研究PD对脂多糖（LPS）诱导的H9c2细胞和脓毒症大鼠模型的作用及其作用机制，并探讨PD上调的沉默调节蛋白（SIRT）6的作用。LPS诱导的H9c2细胞用于模拟败血症。盲肠结扎穿刺（CLP）诱导的大鼠败血症用于验证PD的保护作用。ELISA，western blotting，免疫荧光，免疫组织化学和流式细胞仪用于研究PD对败血性心肌损伤的保护机制。PD预处理通过促进SIRT6介导的自噬抑制LPS诱导的H9c2细胞凋亡。SIRT6的下调或自噬的抑制逆转了PD对LPS诱导的细胞凋亡的保护作用。PD预处理还抑制LPS诱导的炎症因子表达。CLP诱导的脓毒症表明，PD预处理可降低CLP诱导的心肌细胞凋亡以及血清肿瘤坏死因子-α，白介素（IL）-1β和IL-6的表达。3-甲基腺嘌呤（自噬抑制剂）的预处理阻止了PD对败血症性心肌病的保护作用。PD治疗可提高SIRT6的表达，这证实PD可通过促进SIRT6介导的自噬来减轻败血症性心肌病。