Introduction

Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis.

Objectives

This study highlights the potential of Astragaloside IV(AS) in the treatment of septic cardiomyopathy and provides a reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction.

Methods

Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2^CKO) /DUSP1 transgenic mice (DUSP1/PHB2^TG) were used to generate LPS-induced sepsis models. The pathological mechanism by which AS-IV improves heart injury was detected using cardiac ultrasound, fluorescence staining, transmission electron microscopy, and western blotting. After siRNA treatment of cardiomyocytes with DUSP-1/PHB2, changes in mitochondrial function and morphology were determined using qPCR, western blotting, ELISA, and laser confocal microscopy, and the targeted therapeutic effects of AS-IV were further examined.

Results

SCM treatment leads to severe mitochondrial dysfunction. However, Astragaloside IV (AS) treatment normalizes mitochondrial homeostasis and ER function. Notably, the protective effect was blocked in DUSP1/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2^CKO) but remained unaffected in DUSP1 transgenic mice (DUSP1/PHB2^TG).

Conclusion

This study highlights the potential of AS in the treatment of septic cardiomyopathy and provides a reference for developing cardioprotective drugs targeting DUSP1-PHB2 related mitochondria-ER interaction.

中文翻译：

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黄芪甲苷 IV 通过 DUSP1-Prohibitin 2 介导的线粒体质量控制和 ER 自噬减轻脓毒性心肌损伤

 介绍

脓毒性心肌病 （SCM） 是严重脓毒症患者心肌损伤的一种并发症。

 目标

本研究强调了黄芪甲苷 IV（AS） 治疗脓毒性心肌病的潜力，为开发靶向 DUSP1-PHB2 相关线粒体-ER 相互作用的心脏保护药物提供参考。

 方法

双特异性磷酸酶-1 （DUSP1）/禁止蛋白 2 心肌细胞特异性敲除小鼠 （DUSP1/PHB2^CKO） /DUSP1 转基因小鼠 （DUSP1/PHB2^TG） 生成 LPS 诱导的脓毒症模型。使用心脏超声、荧光染色、透射电子显微镜和蛋白质印迹法检测 AS-IV 改善心脏损伤的病理机制。用 DUSP-1/PHB2 处理心肌细胞 siRNA 后，使用 qPCR、western blotting、ELISA 和激光共聚焦显微镜测定线粒体功能和形态的变化，并进一步检查 AS-IV 的靶向治疗效果。

 结果

SCM 治疗会导致严重的线粒体功能障碍。然而，黄芪甲苷 IV （AS） 治疗使线粒体稳态和 ER 功能正常化。值得注意的是，保护作用在 DUSP1/Prohibitin 2 心肌细胞特异性敲除小鼠 （DUSP1/PHB2^CKO） 中被阻断，但在 DUSP1 转基因小鼠 （DUSP1/PHB2^TG） 中不受影响。

 结论

本研究强调了 AS 治疗脓毒性心肌病的潜力，为开发靶向 DUSP1-PHB2 相关线粒体-ER 相互作用的心脏保护药物提供了参考。