We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-β-synthase (CBS), and hydrogen sulfide (H₂S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H₂S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin–eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia–ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H₂S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H₂S. H₂S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H₂S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

我们的目的是研究 miRNA-377、胱硫醚-β-合酶 (CBS) 和硫化氢 (H ₂ S) 在缺氧缺血性脑病 (HIE) 发展中的作用机制。我们研究了患有 HIE 的人类和患有缺氧缺血性损伤的动物中CBS、H ₂ S 和 miR-377之间的关系。建立胎鼠缺氧缺血性脑损伤动物模型，将胎鼠随机分为对照组、缺氧缺血15 min组（轻度组）和30 min组（中度组）。人类样本是从诊断患有 HIE 的儿童身上采集的。选择健康或无神经系统疾病儿童作为对照组。本研究采用苏木精-伊红 (HE) 染色、实时定量聚合酶链反应 (qRT-PCR)、酶联免疫吸附测定 (ELISA) 和蛋白质印迹法进行。缺氧缺血引起的脑组织病理改变在严重缺氧损伤组中更为严重。与对照组相比，患有 HIE 的胎鼠和人类样本的脑组织和血清中 miRNA-377 表达水平上调。相反，与对照相比，人类和动物样品中的CBS 和 H _{2 S 表达水平均显着降低。我们的研究结果表明，CBS 是 miR-377 的靶基因，可能通过调节 CBS/H 2} S促进 HIE 的发生。H ₂ S 对脑组织缺氧损伤具有保护作用。_{该研究为 H 2} S 在缺氧性脑损伤中的保护作用的潜在机制提供了新的见解，并可能有助于开发 HIE 的新疗法。