miR-194 Original DATA.xls

Hypothermia has been
reported to be effective in protecting the brain in various clinical
conditions, including resuscitation after cardiac arrest and complex
cardiovascular surgery, and is considered to be a promising therapy for stroke. The present study aimed to confirm a
pivotal role for miRNA-194-5p in
deep hypothermia circulation arrest. We
observed a decline in expression of miR-194-5p in the circulation of 21 aortic
dissection patients who underwent deep hypothermia circulatory arrest.
Subsequently, the specific expression, target, and function of miR-194-5p was
investigated using primary neuron culture, polymerase chain reaction, in situ
hybridization, and flow cytometry methods. Our results showed that miR-194-5p
expression was significantly downregulated in neurons subjected to hypothermia and
oxygen-glucose deprivation in
vitro. Cortical neurons transfected with
miR-194-5p mimic exhibited increased death due to oxygen-glucose deprivation.
MiR-194-5p mediated the regulation of neuronal death, which involves the
downregulation of the specific target protein SUMO2, which is a crucial protein
in ischemia tolerance. Collectively, these data highlight the unique role of
miR-194-5p in mediating the deep hypothermia circulation arrest response via the regulation of SUMO2. These
findings suggest that miR-194-5p could be a potential therapeutic target for
intervention in ischemic disease.

已有研究表明，低体温疗法在多种临床场景中可发挥脑保护作用，涵盖心搏骤停后复苏以及复杂心血管手术领域，且被视为脑卒中治疗的极具潜力的方案。本研究旨在明确微小RNA-194-5p（miRNA-194-5p）在深低温停循环中的关键作用。我们在21例接受深低温停循环手术的主动脉夹层患者的循环样本中，观测到miR-194-5p的表达水平显著下降。随后，我们通过原代神经元培养、聚合酶链式反应、原位杂交以及流式细胞术等实验手段，对miR-194-5p的特异性表达、靶标及功能展开研究。体外实验结果显示，在经低体温处理及氧糖剥夺的神经元中，miR-194-5p的表达水平显著下调。转染miR-194-5p模拟物的皮质神经元，在氧糖剥夺条件下的细胞死亡率显著升高。miR-194-5p可介导神经元死亡的调控过程，其机制涉及下调特异性靶标蛋白小泛素样修饰蛋白2（SUMO2）——该蛋白是缺血耐受中的关键分子。综上，本研究数据表明，miR-194-5p可通过调控SUMO2的表达，在深低温停循环应答过程中发挥独特作用。本研究结果提示，miR-194-5p或可成为缺血性疾病干预的潜在治疗靶点。