miR-125b通过ROS/p53通路减轻脓毒症诱导的海马线粒体分裂和认知损伤

Abstract

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis characterized by neuronal injury and cognitive impairment. However, its underlying mechanisms remain unclear. In this study, we investigated the role of miR-125b in sepsis-induced hippocampal injury. A cecal ligation and puncture (CLP) model was established in mice, and miR-125b was overexpressed in the hippocampus using lentiviral vectors. CLP-induced sepsis increased mitochondrial fission and neuronal apoptosis in the hippocampus, accompanied by p53 activation and reduced miR-125b expression. miR-125b overexpression suppressed mitochondrial fission markers, reduced neuronal apoptosis, and improved cognitive deficits. Mechanistically, miR-125b inhibited ROS accumulation and p53 activation, whereas p53 overexpression reversed these protective effects. Conversely, hippocampal knockdown of miR-125b with LV-anti-miR-125b aggravated mitochondrial fission and neuronal apoptosis, further supporting its protective role. These findings indicate that miR-125b protects against sepsis-induced hippocampal injury by regulating the ROS/p53 pathway.