Sirtuin 3 (SIRT3) is critical in mitochondrial function and oxidative stress. Our present study investigates whether hydrogen sulfide (H₂S) attenuated myocardial fibrosis and explores the possible role of SIRT3 on the protective effects. Neonatal rat cardiac fibroblasts were pretreated with NaHS followed by angiotensin II (Ang II) stimulation. SIRT3 was knocked down with siRNA technology. SIRT3 promoter activity and expression, as well as mitochondrial function, were measured. Male wild-type (WT) and SIRT3 knockout (KO) mice were intraperitoneally injected with NaHS followed by transverse aortic constriction (TAC). Myocardium sections were stained with Sirius red. Hydroxyproline content, collagen I and collagen III, α-smooth muscle actin (α-SMA), and dynamin-related protein 1 (DRP1) expression were measured both in vitro and in vivo. We found that NaHS enhanced SIRT3 promoter activity and increased SIRT3 mRNA expression. NaHS inhibited cell proliferation and hydroxyproline secretion, decreased collagen I, collagen III, α-SMA, and DRP1 expression, alleviated oxidative stress, and improved mitochondrial respiration function and membrane potential in Ang II-stimulated cardiac fibroblasts, which were unavailable after SIRT3 was silenced. In vivo, NaHS reduced hydroxyproline content, ameliorated perivascular and interstitial collagen deposition, and inhibited collagen I, collagen III, and DRP1 expression in the myocardium of WT mice but not SIRT3 KO mice with TAC. Altogether, NaHS attenuated myocardial fibrosis through oxidative stress inhibition via a SIRT3-dependent manner.

中文翻译：

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硫化氢通过 Sirtuin 3 的氧化应激抑制减弱血管紧张素 II 诱导的心脏成纤维细胞增殖和横向主动脉缩窄诱导的心肌纤维化

Sirtuin 3 (SIRT3) 对线粒体功能和氧化应激至关重要。我们目前的研究调查硫化氢 (H ₂ S) 是否能减轻心肌纤维化，并探讨 SIRT3 对保护作用的可能作用。用 NaHS 预处理新生大鼠心脏成纤维细胞，然后进行血管紧张素 II (Ang II) 刺激。SIRT3 被 siRNA 技术击倒。测量了 SIRT3 启动子的活性和表达，以及线粒体功能。雄性野生型 (WT) 和 SIRT3 敲除 (KO) 小鼠腹膜内注射 NaHS，然后进行横向主动脉缩窄 (TAC)。心肌切片用天狼星红染色。羟脯氨酸含量、胶原蛋白 I 和胶原蛋白 III、α-平滑肌肌动蛋白 ( α-SMA) 和 dynamin 相关蛋白 1 (DRP1) 表达在体外和体内进行了测量。我们发现 NaHS 增强了 SIRT3 启动子的活性并增加了 SIRT3 mRNA 的表达。NaHS 抑制细胞增殖和羟脯氨酸分泌，降低胶原蛋白 I、胶原蛋白 III、α- SMA 和 DRP1 的表达，缓解氧化应激，改善 Ang II 刺激的心脏成纤维细胞的线粒体呼吸功能和膜电位，这些在 SIRT3 沉默后不可用. 体内, NaHS 降低羟脯氨酸含量，改善血管周围和间质胶原沉积，并抑制 WT 小鼠心肌中的胶原蛋白 I、胶原蛋白 III 和 DRP1 表达，而不是 TAC 的 SIRT3 KO 小鼠。总之，NaHS 通过 SIRT3 依赖的方式通过氧化应激抑制来减轻心肌纤维化。