Objective To investigate the effect of gastrodin on hippocampal cell ferroptosis of rats with vascular dementia (VaD) and its mechanism. Methods Sixty male SD rats were randomly divided into sham group,model group,low-dose gastrodin group (25 mg/kg),high-dose gastrodin group (50 mg/kg) and donepezil group (2 mg/kg,positive control) . Rat VaD model was established by permanent middle cerebral artery occlusion in model group,low-dose gastrodin group,high-dose gastrodin group and donepezil group. Sham group was given the same procedures as model group except for not occluding the middle cerebral artery. At 1 week after modeling,the rats in each treatment group were intragastrically administered,while model group and sham group were intragastrically administered with corresponding volumes of distilled water. The treatment lasted for 8 consecutive weeks. Morris water maze was performed to record the escape latency and the times of crossing platforms in each group. At the end of Morris water maze,the contents of malondialdehyde ( MDA),reduced glutathione ( GSH ),and Fe2+in rat the hippocampal tissues in each group were detected,and the protein expressions of ferroptosis marker proteins GPX4 and COX2 were detected by Western blot and immunohistochemistry. Results When compared with model group,high-dose gastrodin and donepezil groups had significantly shorten escape latency ( P<0.05 ) and increased times of crossing platforms (P<0.05). When compared with model group,high-dose gastrodin and donepezil groups had decreased levels of MDA and Fe2+in rat hippocampi (P<0.05) and increased GSH activity (P<0.05). When compared with model group,high-dose gastrodin and donepezil groups had significantly upregulated GPX4 protein expression and downregulated COX2 protein expression. Conclusion Gastrodin can improve the learning and memory ability of rat with VaD model,and its mechanism may be related to the reduction of Fe2+accumulation in rat hippocampi,the inhibition of hippocampal cell ferroptosis,and the protection of hippocampal neurons in rats with VaD.
维普
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