Effect of oxymatrine on hypoxic-ischemic brain injury in neonatal rats

Abstract

Purpose: To study the influence of oxymatrine on hypoxic-ischemic brain injury (HIBI) in neonatal rats. Methods: Newborn SPF Sprague-Dawley (SD) rats were randomly assigned to 3 groups (10 rats/group): control, HIBI and oxymatrine groups. Neurobehavioral latency of each rat was determined after 48 h of treatment, and pathological changes in rat cerebral cortex were evaluated using H&E staining. Hippocampal neurons prepared from rat brain tissue were grouped and treated as per the above in vivo study. Cell survival and neuronal apoptotic changes were measured with CCK-8 and flow cytometric analysis, respectively, while protein expressions of bcl-2, mcl-1, bax, caspase-3, PI3K, p- PI3K, Akt, p-Akt, GSK3β and p-GSK3β were determined with Western blotting. Results: Treatment of HIBI rats with oxymatrine significantly reduced their neurobehavioral latencies (reflex, cliff avoidance reflex, and negative reflex (latencies), but repaired HIBI-induced histological damage in rat cerebral cortex (p < 0.05). It also significantly enhanced the survival of rat hippocampal neurons, while reducing neuronal apoptosis (p < 0.05). Moreover, oxymatrine significantly upregulated bcl-2, mcl-1, p-PI3K, AKT, p-AKT, GSK3β and p-GSK3β protein expressions, but i significantly downregulated the protein expressions of bax and caspase-3 in cerebral cortex of HIBI rat (p < 0.05). Conclusion: These results indicate that oxymatrine reduces neuronal apoptosis and alleviates HIBI in rats via the regulation of proteins associated with PI3K/Akt/GSK3β signal pathway. This finding provides a new research direction on novel botanical monomers for treating HIBI.