Department of Anesthesiology, Chongqing General Hospital, University of Chinese Academy of Sciences, 312 Zhongshan Road, Chongqing 400013, China.
Department of Anesthesiology, Chongqing General Hospital, University of Chinese Academy of Sciences, 312 Zhongshan Road, Chongqing 400013, China.
Life Sci. 2020 Nov 1;260:118315. doi: 10.1016/j.lfs.2020.118315. Epub 2020 Aug 22.
Cardiac dysfunction is the main cause of multi-organ failure following sepsis within critical care units. The present study aimed to investigate the effects of the small molecule inhibition of cyclic GMP-AMP synthase (cGAS), RU.521, on cardiac function in mice with sepsis.
Sepsis was induced in mice via intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg, i.p.). Mice subsequently received 5 mg/kg RU.521 within 10 min form LPS injection. The cardiac function, inflammatory factor and oxidative stress of mice were examined for 24 h following LPS injection.
RU.521 was indicated to significantly increase the cardiac function of mice with sepsis. In addition, the inflammatory responses, oxidative stress and apoptosis in hearts of sepsis mice were markedly mitigated by RU.521. Moreover, inhibition of Sirt3 inhibited the protective effects of RU.521 on mice with sepsis.
The current study indicated that RU.521 alleviated the inflammatory response and alleviated the damage induced by oxidative stress, leading to cardiac protection via increased Sirt3 expression in the hearts of mice with sepsis.
心功能障碍是重症监护病房脓毒症导致多器官衰竭的主要原因。本研究旨在探讨小分子抑制环鸟苷酸-腺苷酸合酶（cGAS）、RU.521 对脓毒症小鼠心功能的影响。
通过腹腔内脂多糖（LPS）注射（10mg/kg，ip）诱导小鼠脓毒症。LPS 注射后 10min 内，小鼠给予 5mg/kg RU.521。注射 LPS 后 24h 检测小鼠心功能、炎症因子和氧化应激。
RU.521 显著增加脓毒症小鼠的心功能。此外，RU.521 明显减轻脓毒症小鼠心脏的炎症反应、氧化应激和细胞凋亡。此外，沉默信息调节因子 3（Sirt3）的抑制作用抑制了 RU.521 对脓毒症小鼠的保护作用。
本研究表明，RU.521 通过增加脓毒症小鼠心脏中的 Sirt3 表达，减轻炎症反应，缓解氧化应激引起的损伤，从而对脓毒症小鼠的心脏起到保护作用。
