The Role of Cystathionine-β-Synthase, H 2 S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-β-synthase (CBS), and hydrogen sulfide (H2 S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2 S, 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 H2 S 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/H2 S. H2 S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2 S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.