吲哚布芬通过抑制NF-κB/Caspase-1/GSDMD通路减轻脑缺血再灌注损伤的作用与机制研究OA

Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models.However,its therapeutic potential and mechanisms against cerebral ischemia/reperfusion(I/R)injury remain unclear.In this study,we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion(MCAO/R).In vitro,human umbilical vein endothelial cells(HUVECs)subjected to oxygen-glucose deprivation/reoxygenation(OGD/R)were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway.The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2(TXB2),infarct size,b rain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs.The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway.Overall,these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.