Impact of rAAV-VEGF_(165) gene introduced with different pathways on the express ion of vascular endothelial growth factor in cerebral ische-mic penumbra in rats

BACKGROUND:VEGF gene promote the growth of blood vessel.Which introducing path way achieve a more ideal expression remains further discussion. OBJECTIVE:To investigate the impact of rAAV-VEGF165 gene transferred through both intravenous route and cerebrospinal fluid(CSF) route on the expression of v ascular endothelial growth factor(VEGF) in cerebral ischemic penumbra for provid ing a laboratorial gist in the VEGF gene therapy in cerebral ischemia. DESIGN:A factorial design. SETTINGS and MATERIALS:Study was conducted in the animal laboratorial center o f Shenzhen People's Hospital and the Department of Pathology of Medical College of Jinan University.Forty-eight male SD rats in a SPF grade were selected. INTERVENTION:A model of permanent middle cerebral artery occlusion(MACO) was e stablished by nylon suture embolization and cerclage in SD rats. Forty-eight SD rats were randomly divided into CSF route group,intravenous route group, infarc t group and sham-operation group.The rAAV-VEGF165 gene was transferred through CSF injection or intravenous injection within 24 hours in the therapy groups.On the 7th and 14th day,the brains of the six rats from each group were removed af ter the animals were executed for immunohistochemical analysis to detect the exp ression of VEGF gene in ischemic penumbra(IP). MAIN OUTCOME MEASURES:The density of the VEGF Immunoreactive(IR)-positive cel l in the cerebral tissue over time in the rats from each group. RESULTS:The numbers of rats finally entered into statistical analysis were fou r groups with 12 rats each without any loss.The density of VEGF-IR-positive ce ll(under high power field,×400) in cerebral IP of each group at the 7th day was 74.90±2.33 in CSF group,36.27±2.61 in intravenous group,24.27±1.69) in infar ct group and 5.65±0.47 in sham-operation group respectively(P 0.05);and at th e 14th day was 95.03±1.55 in CSF group,69.71±4.29 in intravenous group, 29.95 ±1.05 in infarct group and 7.30±0.76 in sham-operation group respectively(P 0.05). CONCLUSION:Under the mediation of rAAV,VEGF165 gene can be transfected into th e cerebral ischemic tissue through both CSF route and intravenous route to expre ss VEGF,which can promote the formation of new vessels and protect neurocytes to treat cerebral ischemia.