Effect of Silencing Information Regulator on Rat Cerebral Venous Thrombosis Through Regulating Vascular Endothelial Growth Factor

Abstract

Cerebral venous thrombosis (CVST) can cause severe dysfunction and even death. Silencing information regulator (SIRT1) involves in neurodegenerative diseases. However, whether SIRT1 participates in CVST is unclear. SD rats were divided into 3 groups, control group; CVST group and SIRT1 group (transfected with AAV-SIRT1 plasmid) followed by analysis of brain tissue SIRT1 and VEGF expression by Real time PCR, neurological deficit scores and brain tissue water content. Brain vascular endothelial cells (bVECs) were cultured and divided into NC group, SIRT1 group and si-SIRT1 group followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, SIRT1 expression by Real time PCR and Western blot and VEGF expression and secretion by Real time PCR and ELISA. SIRT1 expression was decreased and VEGF expression was increased, along with increased score of neurological deficit and water content of brain tissue in CVST rats. Transfection of AAV-SIRT1 plasmid up-regulated SIRT1 expression in CVST rats, inhibited VEGF expression, improved neurological deficit score and brain tissue water content (P < 0.05). Overexpression of SIRT1 in bVECs significantly decreased cell proliferation, elevated Caspase 3 activity, and decreased VEGF expression and secretion, compared to NC group (P < 0.05). Knockdown of SIRT1 expression in bVECs reversed the above changes (P < 0.05). SIRT1 expression is decreased in CVST rats and up-regulation of SIRT1 can inhibit VEGF expression and improve neurological function. SIRT1 can inhibit the proliferation of bVECs and regulate cerebral venous thrombosis by regulating VEGF.