载脂蛋白E基因与缺血性卒中后脑损伤关系的研究进展OA

The apolipoprotein E(APOE)gene and its encoded protein ApoE represent promising targets worthy of attention in studies of brain cytoprotection for ischemic stroke.The ApoE protein is involved in pathophysiological processes closely linked to tissue injury and repair after cerebral ischemia,including cerebral lipid transport,glia-neuron support,regulation of inflammatory responses,and maintenance of the neurovascular unit and the blood-brain barrier homeostasis.Preclinical studies have demonstrated that endogenous ApoE deficiency in Apoe gene knockout mice aggravates experimental ischemic brain injury.Humanized APOE2,APOE3,and APOE4 knock-in mouse models further indicate that mice expressing the human ApoE4 protein isoform may develop more severe cerebral infarction and neurological deficits.In addition,interventional studies have verified that ApoE mimetic peptides CN-105 and COG1410 exert effects of regulating inflammatory responses,stabilizing the blood-brain barrier,and improving neurological function in animal models of ischemic stroke.Clinical studies have yielded inconsistent findings regarding the associations between APOE genotype and ischemic stroke risk,age at onset,short-term functional outcomes,and post-stroke cognitive outcomes.Current evidence is insufficient to support APOE genotype as an independent predictive biomarker or a well-established therapeutic target for ischemic stroke.This review summarizes the potential mechanisms,preclinical and clinical research evidence regarding the APOE gene and ApoE protein-related pathways in post-ischemic brain injury,as well as therapeutic strategies targeting ApoE-associated pathways.