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Exosomes Protect Against Acute Myocardial Infarction in Rats by Regulating the Renin-Angiotensin System
Stem Cells and Development ( IF 2.5 ) Pub Date : 2021-06-08 , DOI: 10.1089/scd.2020.0132
Mengyuan Xiao 1 , Weikai Zeng 1 , Junxian Wang 2 , Feng Yao 1 , Zijian Peng 1 , Guangyan Liu 2 , Liqin Yu 1 , Wenyan Wei 2 , Shengzhi Zhou 1 , Kaize Li 1 , Luyao Wu 1 , Kunpeng Zhu 1 , Yuejie Guan 2 , Huanyu Chen 3 , Zhenjun Liu 1 , Jianying Chen 1
Affiliation  

The renin-angiotensin system (RAS) has been suggested to play an important role in cardiac remodeling after acute myocardial infarction (AMI). We have confirmed that bone marrow mesenchymal stem cell-derived exosomes (BMSC-EX) had similar types of repair like effects upon tissues as BMSC, but the mechanisms remain unknown. BMSC were cultured to the third generation and were induced to release exosomes. Rats were injected with exosomes (100 μg/mL) or stem cells (1 × 106/mL) through the tail vein immediately after AMI was built, compared to those treated with physiological saline. Thereafter, all groups were analyzed for cardiac function, infarction sizes, and the levels of expression of BNP, ACE, ACE2, AngII, Ang1-7, and other factors in the plasma. After H2O2 makes contact with H9C2 cardiomyocytes, cell proliferation activity and apoptotic rates were measured by using CCK8 kits, to facilitate investigation of the effect of exosomes on H9C2 cells. In vivo, the index of cardiac remodeling and cardiac function was improved in both groups of exosomes and stem cells after AMI. Furthermore, exosomes may have helped to regulate the balance of the RAS system, upregulate ACE2—Ang1-7—Mas, and downregulate the ACE—AngII—ATIR pathway. Therefore, its effects were such as to accelerate the conversion of Ang II to Ang 1-7, thereby improving cardiac remodeling and forming sustained myocardial protection. In vitro, exosomal intervention was found to have increased the levels of activity of H9C2 cardiomyocytes under H2O2 injury and improved adverse effects of AngII upon H9C2 cells. All procedures for this study were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at Guangdong Medical University. BMSC-EX improved cardiac remodeling and cardiac function, and had effects upon RAS system-related factors in plasma. Similarly, BMSC-EX also helped to protect H9C2 cells under attack from H2O2 or AngII, and may thus play beneficial roles by facilitating regulation of the balance of the RAS system.

中文翻译:

外泌体通过调节肾素-血管紧张素系统预防大鼠急性心肌梗死

肾素-血管紧张素系统 (RAS) 在急性心肌梗死 (AMI) 后的心脏重塑中发挥重要作用。我们已经证实,骨髓间充质干细胞衍生的外泌体 (BMSC-EX) 对组织具有与 BMSC 类似的修复样作用,但其机制仍然未知。BMSC培养至第三代并诱导释放外泌体。与用生理盐水处理的大鼠相比,在AMI建立后立即通过尾静脉向大鼠注射外泌体(100μg/mL)或干细胞(1×10 6 /mL)。此后,分析所有组的心功能、梗死面积以及血浆中BNP、ACE、ACE2、AngII、Ang1-7等因子的表达水平。H 2 O 2后与H9C2心肌细胞接触,使用CCK8试剂盒测量细胞增殖活性和凋亡率,以促进外泌体对H9C2细胞的影响研究。在体内,AMI后两组外泌体和干细胞的心脏重塑和心脏功能指数均得到改善。此外,外泌体可能有助于调节 RAS 系统的平衡,上调 ACE2-Ang1-7-Mas,并下调 ACE-AngII-ATIR 通路。因此,其作用是加速Ang II向Ang 1-7的转化,从而改善心脏重构,形成持续的心肌保护作用。在体外,发现外泌体干预增加了H 2 O 2下H9C2心肌细胞的活性水平AngII 对 H9C2 细胞的损伤和改善的副作用。本研究的所有程序均经广东医科大学机构动物护理和使用委员会 (IACUC) 审查和批准。BMSC-EX 改善了心脏重塑和心脏功能,并对血浆中的 RAS 系统相关因子产生了影响。同样,BMSC-EX 也有助于保护 H9C2 细胞免受 H 2 O 2或 AngII 的攻击,因此可能通过促进 RAS 系统平衡的调节发挥有益作用。
更新日期:2021-06-09
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