BACKGROUND Sepsis, a life-threatening systemic syndrome related to inflammatory response, usually accompanied by major organ dysfunctions. The aim of the present study was to elucidate the role by which Shengmai injection (SMI) acts to septic cardiomyopathy. METHODS Initially, the induced mice with septic cardiomyopathy were treated with SMI or normal saline (NS) with oe-caspase-3, and HL-1 cells were treated with oe-Beclin-1 and oe-caspase-3 and then cultured with lipopolysaccharide (LPS). Subsequently, we measured the cardiac troponin I (cTnI) level, and expression of mitochondrial autophagy protein (parkin and pink1) and myocardial cell autophagy-related proteins (LC3-II and LC3-I). Additionally, we identified the cleavage of Beclin-1 by caspase-3 and detected the changes of mitochondrial membrane potential, level of reactive oxygen species (ROS), and apoptosis of myocardial cells in myocardial tissues of mice. RESULTS It has been demonstrated that SMI contributed to the increase of myocardial mitochondrial autophagy, reduction of cTnI level, and elevation of mitochondrial membrane potential in septic cardiomyopathy mice. Both in vitro and in vivo experiments showed that caspase-3 promoted cleavage of Beclin-1 and release of ROS, whereas repressed lipopolysaccharide (LPS)-induced mitochondrial autophagy. Furthermore, the facilitation of myocardial mitochondrial autophagy and protection of myocardial mitochondria by SMI through inhibition of cleavage Beclin-1 by caspase-3 in septic cardiomyopathy mice were also proved by in vivo experiments. CONCLUSION Taken together, SMI could protect myocardial mitochondria by promoting myocardial mitochondrial autophagy in septic cardiomyopathy via inhibition of cleavage of Beclin-1 by caspase-3. Our study demonstrates that SMI could represent a novel target for treatment of septic cardiomyopathy.

中文翻译：

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生脉注射液通过 caspase-3/Beclin-1 轴诱导心肌线粒体自噬对小鼠脓毒性心肌病的保护作用。

背景技术脓毒症是一种与炎症反应相关的危及生命的全身综合征，通常伴有主要器官功能障碍。本研究的目的是阐明生脉注射液 (SMI) 对脓毒性心肌病的作用。方法首先对诱导的脓毒性心肌病小鼠进行SMI或生理盐水（NS）和oe-caspase-3处理，HL-1细胞用oe-Beclin-1和oe-caspase-3处理，然后用脂多糖培养。 （脂多糖）。随后，我们测量了心肌肌钙蛋白 I (cTnI) 水平，以及线粒体自噬蛋白（parkin 和 pink1）和心肌细胞自噬相关蛋白（LC3-II 和 LC3-I）的表达。此外，我们还鉴定了 caspase-3 对 Beclin-1 的切割，并检测了线粒体膜电位的变化，小鼠心肌组织中活性氧（ROS）水平和心肌细胞凋亡。结果 已证明 SMI 有助于增加脓毒性心肌病小鼠的心肌线粒体自噬、cTnI 水平降低和线粒体膜电位升高。体外和体内实验均表明，caspase-3 促进 Beclin-1 的裂解和 ROS 的释放，同时抑制脂多糖 (LPS) 诱导的线粒体自噬。此外，体内实验也证明了SMI通过抑制caspase-3对Beclin-1的裂解促进心肌线粒体自噬和保护心肌线粒体。结论 综上所述，SMI 可通过抑制 caspase-3 对 Beclin-1 的切割，促进败血性心肌病心肌线粒体自噬，从而保护心肌线粒体。我们的研究表明，SMI 可以代表治疗脓毒性心肌病的新靶点。