Department of Anesthesiology, the First Hospital of the PLA, Lanzhou 730031, PR China.
Department of Anesthesiology, the First Hospital of Lanzhou University, Donggang Courtyard Area, Lanzhou 730030, PR China.
Biomed Pharmacother. 2019 May;113:108697. doi: 10.1016/j.biopha.2019.108697. Epub 2019 Mar 9.
Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway.
心肌缺血/再灌注损伤（IRI）长期以来被认为是心肌缺血、心脏手术或循环骤停后不良心血管结局的一个促成因素。本研究旨在探讨七氟醚预处理（SAP）后靶向 perilipin-5（PLIN5）的 microRNA（miR-370）对小鼠的影响。建立了左心室心肌 IRI 小鼠模型，随后评估心肌梗死面积和心功能，以确定 SAP 的影响。分析了 miR-370 与 SAP 处理的 IRI 小鼠分离的心肌细胞中 miR-370 模拟物、miR-370 抑制剂或 PLIN5 的 siRNA 治疗相结合的潜在调节机制。此外，还评估了治疗后心肌细胞的增殖、细胞周期分布和凋亡。最后，向 SAP 处理的 I/R 小鼠注射 miR-370 抑制剂以验证 SAP 的机制。SAP 对心肌 IRI 具有心脏保护作用。在发生 IRI 的小鼠中，miR-370 下调，但 SAP 可上调 miR-370 的表达。功能上，miR-370 负向靶向 PLIN5 并激活过氧化物酶体增殖物激活受体（PPAR）信号通路，导致 PPARγ 表达降低但 PPARα 表达增加。结果还表明，miR-370 或 PLIN5 的沉默可促进心肌细胞增殖。miR-370 还通过降低 caspase-3 表达和增加 Bcl-2 表达抑制心肌细胞凋亡。此外，SAP 还通过抑制 PPARγ 缓解 I/R 损伤。本研究表明，SAP 诱导 miR-370 并对心肌 IRI 发挥心脏保护作用，上调 miR-370 通过抑制 PLIN5 依赖性 PPAR 信号通路减轻心肌 IRI。
