Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling
Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling
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DOI：
10.1007/s11033-023-08250-6
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发表时间：
2023-01
影响因子：
2.8
通讯作者：
Yanting Sun;Hao Xu;B. Tan;Qin Yi;Huiwen Liu;Jie Tian;Jing Zhu
中科院分区：
文献类型：
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作者：
Yanting Sun;Hao Xu;B. Tan;Qin Yi;Huiwen Liu;Jie Tian;Jing Zhu
骨髓间充质干细胞（BMSCs）移植治疗为心肌缺血性缺氧损伤的恢复提供了很大的希望。然而，心肌损伤后的微环境不利于骨髓间充质干细胞的存活，限制了骨髓间充质干细胞的治疗应用。我们之前的研究证实，经穿心术内酯（Andrographolide， AG）预处理后，骨髓间充质干细胞在缺氧下葡萄糖和血清剥夺（GSDH）下的存活率增加，但这种处理是否能提高骨髓间充质干细胞修复心肌损伤的作用尚未得到证实。方法和结果首先用GSDH处理H9C2，模拟体外心肌损伤微环境，然后用AG预处理大鼠原代骨髓间充质干细胞，收集GSDH处理后的骨髓间充质干细胞条件培养基（BMSCs- cm）和经AG预处理的骨髓间充质干细胞条件培养基（AG-BMSCs- cm）。并将其用于GSDH下处理H9C2细胞，进一步检测氧化应激和代谢变化。结果表明，AG-BMSCs-CM比BMSCs-CM更有利于心肌细胞损伤修复，表现为细胞凋亡率和氧化应激的降低。线粒体和脂滴的变化结果表明AG-BMSCs-CM可以调节H9C2细胞的代谢重塑，修复细胞损伤，AMPK在此过程中被激活。结论本研究首次证实了AG-BMSCs-CM对gsdh诱导心肌细胞损伤的保护作用，为临床应用提供了潜在的治疗策略。
BackgroundBone marrow mesenchymal stem cells (BMSCs) transplantation therapy providing a great hope for the recovery of myocardial ischemic hypoxic injury. However, the microenvironment after myocardial injury is not conducive to the survival of BMSCs, which limits the therapeutic application of BMSCs. Our previous study has confirmed that the survival of BMSCs cells in the glucose and serum deprivation under hypoxia (GSDH) is increased after Andrographolide (AG) pretreatment, but whether this treatment could improve the effect of BMSCs in repairing of myocardial injury has not been verified.Methods and resultWe first treated H9C2 with GSDH to simulate the microenvironment of myocardial injury in vitro, then we pretreated rat primary BMSCs with AG, and collected conditioned medium derived from BMSCs (BMSCs-CM) and conditioned medium derived from AG-pretreated BMSCs (AG-BMSCs-CM) after GSDH treatment. And they were used to treat H9C2 cells under GSDH to further detect oxidative stress and metabolic changes. The results showed that AG-BMSCs-CM could be more advantageous for cardiomyocyte injury repair than BMSCs-CM, as indicated by the decrease of apoptosis rate and oxidative stress. The changes of mitochondria and lipid droplets results suggested that AG-BMSCs-CM can regulate metabolic remodeling of H9C2 cells to repair cell injury, and that AMPK was activated during this process.ConclusionsThis study demonstrates, for the first time, the protective effect of AG-BMSCs-CM on GSDH-induced myocardial cell injury, providing a potential therapeutic strategy for clinical application.