Endoplasmic reticulum (ER) stress-mediated apoptosis pathway is considered to play a vital role in mediating stroke and other cerebrovascular diseases. Previous studies have showed that vascular endothelial growth factor (VEGF) antagonism reduced cerebral ischemic/reperfusion (CI/R) damage， but whether attenuation of ER stress-induced apoptosis is contributing to its mechanisms remains elusive. Our study aimed to investigate the protective effect of VEGF antagonism on CI/R-induced injury. First， oxygen-glucose deprivation and re-oxygenation (OGD/R) BEND3 cell model was constructed to estimate siRNA-VEGF on damage of endothelial cells. Next， in animal model， CI/R mice were induced by middle cerebral arte... More
Endoplasmic reticulum (ER) stress-mediated apoptosis pathway is considered to play a vital role in mediating stroke and other cerebrovascular diseases. Previous studies have showed that vascular endothelial growth factor (VEGF) antagonism reduced cerebral ischemic/reperfusion (CI/R) damage， but whether attenuation of ER stress-induced apoptosis is contributing to its mechanisms remains elusive. Our study aimed to investigate the protective effect of VEGF antagonism on CI/R-induced injury. First， oxygen-glucose deprivation and re-oxygenation (OGD/R) BEND3 cell model was constructed to estimate siRNA-VEGF on damage of endothelial cells. Next， in animal model， CI/R mice were induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion to investigate cerebral tissue damage. For treatment group， mice received 100 µg/kg anti-VEGF antibodies at 30 min before MCAO， followed by 24 h reperfusion. Our findings demonstrated that pre-administration of siRNA-VEGF before OGD/R changed the biological characteristics of BEND3 cells， reversed the levels of X-box binding protein-1 (XBP-1) and glucose-regulated protein 78 (GRP78)， showing siRNA-VEGF attenuated， at least in part， the oxidative damage in OGD/R cell by down-regulating ER stress. In mice experiment， pre-administration of anti-VEGF antibody reduced the brain infarct volume and edema extent and improved neurological scores outcome of CI/R injury mice. Pathological and TUNEL staining results also confirmed this protective effect. The expressions of VEGF， CATT/EBP homologous protein (CHOP)， inositol requiring enzyme 1α (IRE-1α)， and cleaved-caspase12 and jun N-terminal kinase (JNK) phosphorylation were also prominently decreased. These results suggested that inhibition of endogenous VEGF attenuates CI/R-induced injury via inhibiting ER stress-mediated apoptosis.
