Aims. The aim of this study was to investigate whether resveratrol (RSV) could ameliorate ischemia- and hypoxia-associated cardiomyocyte apoptosis and injury via inhibiting senescence signaling and inflammasome activation. Materials and Methods. Mice were treated with RSV by gastric tube (320 mg/kg/day) or vehicle one week before left coronary artery ligation or sham surgery until the end of the experiments. After pressure–volume loop analysis, mouse hearts were harvested for histopathological (including PSR, TTC, TUNEL staining, immunohistochemistry, and immunofluorescence) and molecular analysis by western blotting and RT-PCR. In addition, neonatal rat cardiomyocytes (NRCMs), cardiac fibroblasts (CFs), and macrophages were isolated for in vitro experiments. Key Findings. RSV treatment decreased mortality and improved cardiac hemodynamics. RSV inhibited the expression of senescence markers (p53, p16, and p19), inflammasome markers (NLRP3 and Cas1 p20), and nuclear translocation of NF-κB, hence alleviating infarction area, fibrosis, and cell apoptosis. RSV also inhibited expression of interleukin- (IL-) 1β, IL-6, tumor necrosis factor-α, and IL-18 in vivo. In in vitro experiment, RSV prevented hypoxia-induced NRCM senescence and apoptosis. After inhibition of sirtuin 1 (Sirt1) by EX27, RSV failed to inhibit p53 acetylation and expression. Moreover, RSV could inhibit expression of NLRP3 and caspase 1 p20 in NRCMs, CFs, and macrophages, respectively, in in vitro experiments. Significance. Our findings revealed that RSV protected against ischemia-induced mouse heart injury in vivo and hypoxia-induced NRCM injury in vitro via regulating Sirt1/p53-mediated cell senescence and inhibiting NLRP3-mediated inflammasome activation.

中文翻译：

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白藜芦醇抑制缺血诱导的心肌衰老信号和 NLRP3 炎性体激活。

目标。本研究的目的是研究白藜芦醇 (RSV) 是否可以通过抑制衰老信号和炎症小体激活来改善缺血和缺氧相关的心肌细胞凋亡和损伤。材料和方法。在左冠状动脉结扎或假手术前一周，通过胃管（320 mg/kg/天）或载体用 RSV 治疗小鼠，直到实验结束。在压力-容积环分析后，收获小鼠心脏进行组织病理学（包括 PSR、TTC、TUNEL 染色、免疫组织化学和免疫荧光）和蛋白质印迹和 RT-PCR 的分子分析。此外，分离出新生大鼠心肌细胞 (NRCMs)、心脏成纤维细胞 (CFs) 和巨噬细胞用于体外实验。主要发现。RSV 治疗降低了死亡率并改善了心脏血流动力学。RSV 抑制衰老标志物（p53、p16 和 p19）、炎性体标志物（NLRP3 和 Cas1 p20）的表达以及 NF-κB 的核转位，从而减轻梗死面积、纤维化和细胞凋亡。RSV 还在体内抑制白细胞介素 (IL-) 1 β、IL-6、肿瘤坏死因子-α和 IL-18的表达。在体外实验表明，RSV 可阻止缺氧诱导的 NRCM 衰老和凋亡。在 EX27 抑制 sirtuin 1 (Sirt1) 后，RSV 未能抑制 p53 乙酰化和表达。此外，在体外实验中，RSV 可以分别抑制 NRCM、CF 和巨噬细胞中 NLRP3 和 caspase 1 p20 的表达。意义。我们的研究结果表明，RSV 通过调节 Sirt1/p53 介导的细胞衰老和抑制 NLRP3 介导的炎性体激活，在体内保护缺血诱导的小鼠心脏损伤和体外缺氧诱导的 NRCM 损伤。