丁酸钠通过抑制JNK/STAT通路缓解小鼠脑缺血再灌注损伤

Abstract

Objective: The aim of this study was to investigate whether sodium butyrate (NaB) attenuated cerebral ischemia-reperfusion injury (IRI) in mice by inhibiting JNK/STAT pathway, thereby exerting a neuroprotective role. Materials and methods: ICR mice were randomly assigned into five groups, including the sham group, the model group, the 1 mg/kg NaB group, the 5 mg/kg NaB group and the 10 mg/kg NaB group, respectively. IRI model was established in mice using the bilateral common carotid artery occlusion (BCCAO) method. Open-field test was performed to evaluate degree of IRI damage by recording central travel distance and central active time. The morphology of hippocampal neurons was observed by hematoxylin and eosin (HE) staining. TUNEL staining was conducted to detect apoptotic neurons in the brain of mice. Meanwhile, activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues of mice were determined by relative commercial kits. The expression levels of inflammatory factors in brain tissues of mice were accessed using enzyme-linked immunosorbent assay (ELISA). In addition, the protein expressions of Jak2 and STAT3 in brain tissues of mice were detected by Western blot. Results: 10 mg/kg NaB treatment remarkably alleviated impaired neurological defect and hippocampal neurons, as well as significantly improved neuronal survival. Mice in the 10 mg/kg NaB group showed significantly lower central travel distance and shorter central active time than those in the sham group. In addition, 10 mg/kg NaB treatment markedly increased SOD activity, whereas significantly decreased MDA activity in IRI mice. Mice in the NaB treatment group showed significantly lower levels of IL-1β, TNF-α and IL-8. Meanwhile, TUNEL-positive neurons in mice of the NaB treatment group were remarkably fewer. In addition, the protein expression levels of Jak2 and STAT3 were obviously upregulated in IRI mice, which were significantly downregulated after 10 mg/kg NaB treatment. Con