The Role of Cystathionine-β-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

Abstract

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 15min (mild) and 30min (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.