Anesthetics such as isoflurane are known to cause apoptosis in the developing mammalian brain. However, isoflurane may have protective effects on the heart via relieving ischemia and downregulating genes related to apoptosis. Ischemic preconditioning, e.g. through the use of low levels of carbon monoxide (CO), has promise in preventing ischemia-reperfusion injury and cell death. However, it is still unclear how it either triggers the stress response in neonatal hearts. For this reason, thirty-three microRNAs (miRNAs) known to be differentially expressed following anesthesia and/or ischemic or hypoxic heart damage were investigated in the hearts from neonatal mice exposed to isoflurane or low level of CO, using an air-exposed control group. Only miR-93-5p increased with isoflurane exposure, which may be associated with the suppression of cell death, autophagy, and inflammation. By contrast, twelve miRNAs were differentially expressed in the heart following CO treatment. Many miRNAs previously shown to be responsible for suppressing cell death, autophagy, and myocardial hypertrophy were upregulated (e.g., 125b-3p, 19-3p, and 21a-5p). Finally, some miRNAs (miR-103-3p, miR-1a-3p, miR-199a-1-5p) which have been implicated in regulating energy balance and cardiac contraction were also differentially expressed. Overall, this study demonstrated that CO-mediated miRNA regulation may promote ischemic preconditioning and cardioprotection based on the putative protective roles of the differentially expressed miRNAs explored herein and the consistency of these results with those that have shown positive effects of CO on heart viability following anesthesia and ischemia-reperfusion stress.

已知异氟烷等麻醉剂会导致发育中的哺乳动物大脑细胞凋亡。然而，异氟烷可能通过缓解缺血和下调与细胞凋亡相关的基因对心脏产生保护作用。缺血预处理，例如通过使用低水平的一氧化碳（CO），有望预防缺血再灌注损伤和细胞死亡。然而，目前尚不清楚它如何触发新生儿心脏的应激反应。因此，使用暴露于空气的对照组，对暴露于异氟烷或低水平 CO 的新生小鼠的心脏中的 33 种已知在麻醉和/或缺血或缺氧心脏损伤后差异表达的 microRNA (miRNA) 进行了研究。只有 miR-93-5p 随异氟烷暴露而增加，这可能与细胞死亡、自噬和炎症的抑制有关。相比之下，CO 处理后心脏中 12 种 miRNA 出现差异表达。许多先前被证明负责抑制细胞死亡、自噬和心肌肥大的 miRNA 均被上调（例如 125b-3p、19-3p 和 21a-5p）。最后，一些与调节能量平衡和心脏收缩有关的 miRNA（miR-103-3p、miR-1a-3p、miR-199a-1-5p）也存在差异表达。总体而言，本研究表明，基于本文探讨的差异表达 miRNA 的假定保护作用，CO 介导的 miRNA 调节可能促进缺血预适应和心脏保护，并且这些结果与 CO 对麻醉后心脏活力的积极影响的结果一致和缺血再灌注应激。