Wuhan No 1 Hospital - Department of Anesthesiology - Wuhan (Hubei) - China.
Acta Cir Bras. 2023 Oct 23;38:e383123. doi: 10.1590/acb383123. eCollection 2023.
It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4).
MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated.
MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice.
The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.
已有研究表明，七氟醚（Sevo）在心肌缺血/再灌注损伤（MI/RI）中具有心脏保护作用，并调节控制各种生理系统的 microRNA（miRNA）表达。受此启发，本工作旨在解码七氟醚和 miR-99a 与溴结构域蛋白 4（BRD4）参与的作用机制。
在小鼠中建立 MI/RIModel。MI/RI 模型小鼠暴露于 Sevo 或注射 miR-99a 或 BRD4 相关载体，以鉴定它们在 MI/RI 小鼠心脏功能、病理损伤、心肌细胞凋亡、炎症和氧化应激中的作用。检测心肌组织中 miR-99a 和 BRD4 的表达，并进一步验证它们之间的关系。
MI/RI 小鼠中 miR-99a 下调，BRD4 上调。Sevo 上调 miR-99a 抑制 MI/RI 小鼠心肌组织中 BRD4 的表达。Sevo 改善了 MI/RI 小鼠的心脏功能，减轻了心肌损伤，抑制了心肌细胞凋亡，并缓解了炎症和氧化应激。miR-99a 的恢复进一步增强了 Sevo 对 MI/RI 小鼠的积极作用。BRD4 的过表达逆转了 miR-99a 诱导的 MI/RI 减弱作用。
本研究阐述了 Sevo 通过抑制 BRD4 上调 miR-99a 来减轻 MI/RI。
