Autophagy protects human brain microvascular endothelial cells against methylglyoxal-induced injuries, reproducible in a cerebral ischemic model in diabetic rats

摘要: Cerebral microvascular endothelial cells (ECs) are crucial for brain vascular repair and maintenance, but their physiological function may be impaired during ischemic stroke diabetes. Methylglyoxal (MGO), a reactive dicarbonyl produced glucose metabolism, could exacerbate ischemia-induced EC injury dysfunction. We investigated the protective effect of autophagy on cultured human (HBMEC) that underwent MGO treatment. A further study was conducted to explore underlying mechanisms effect. Autophagic activity assessed by evaluating protein levels, using western blot. 3-methyladenine (3-MA), bafilomycin A1, ammonium chloride (AC), Beclin 1 siRNA, chloroquine (CQ) were used cause inhibition. Alarmar blue assay lactate dehydrogenase release evaluate cell viability. Streptozotocin administered induce type I diabetes in rats post-permanent middle cerebral artery occlusion performed elicit ischemia. Blood-brain barrier permeability also assessed. Our found reduced HBMEC viability concentration- time-dependent manner, triggered responsive activation. Autophagy inhibitors AC, 3-MA, BECN1 siRNA exacerbated MGO-induced injury. FAK phosphorylation inhibitor PF573228 inhibited MGO-triggered enhanced release. Meanwhile, similar activation ECs observed permanent occlusion-induced ischemia diabetic rats, while chloroquine-induced inhibition blood-brain permeability. Taken together, our indicates defends against injuries.