Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through α 7nAChR-Induced Autophagy
摘要Objectives:To evaluate the effect of echinacoside(ECH)on cognitive dysfunction in post cerebral stroke model rats.Methods:The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery(MCAO).The rats were randomly divided into 3 groups by a random number table:the sham group(sham operation),the MCAO group(received operation for focal cerebral ischemia),and the ECH group(received operation for focal cerebral ischemia and ECH 50 mg/kg per day),with 6 rats in each group.The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze.The expression of α 7nAChR in the hippocampus was detected by immunohistochemistry.The contents of acetylcholine(ACh),malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),activities of choline acetyltransferase(ChAT),acetylcholinesterase(AChE),and catalase(CAT)were evaluated by enzyme linked immunosorbent assay.The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining,respectively.Results:ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content(both P<0.01).Compared with MCAO rats,administration of ECH revealed shorter escape latency and long retention time at 7,14 and 28 days(all P<0.01),increased the α7nAChR protein expression,ACh content,and ChAT activity,and decreased AChE activity in MCAO rats(all P<0.01).ECH significantly decreased MDA content and increased the GSH content,SOD,and CAT activities compared with MCAO rats(all P<0.05).ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats(all P<0.01).Conclusion:ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.
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