3-n-butylphthalide (NBP) reduces apoptosis and enhances vascular endothelial growth factor (VEGF) up-regulation in diabetic rats

Abstract

Objective: The aim of this study was to investigate the protective effect of dl-3-n-butylphthalide (NBP) on chronic brain injury caused by diabetes.Methods: A group of diabetic Sprague–Dawley rats was orally treated with NBP for 6 weeks. In this study, we examined glial reactivity in hippocampus of streptozotocin (STZ)-induced diabetic rats by determining the expression of glial fibrillary acidic protein (GFAP) and CD11b. We also examined anti-apoptosis protein, vascular endothelial growth factor (VEGF) and key apoptosis enzyme, caspase-3, expression by immunohistochemistry.Results: We found that GFAP, CD11b, VEGF (685·1 ± 35·5 cells/mm2 in diabetic rats versus 320·6 ± 21·9 cells/mm2 in control rats, p<0·05, n=5) and VEGF+-caspase-3+ (393·4 ± 24·2 cells/mm2 versus 135·8 ± 12·0 cells/mm2 in control rats, p<0·05, n=5) immunostaining increased in the hippocampus of diabetic rats; However, treatment with NBP resulted in an obvious reduction of GFAP and CD11b-immunoreactive gliocytes in hippocampus. VEGF expression was up-regulated (837·2 ± 20·1 cells/mm2, n=5), while the caspase-3 expression was reduced (240·0 ± 15·1 cells/mm2, n=5) in the NBP-treated diabetes mellitus-NBP rats.Conclusion: These results suggest that diabetes causes increased glial reactivity, apoptosis and compensatory VEGF expression, and NBP may have a protective effect for diabetic brain damage through enhancing VEGF expression to inhibit caspase-3 mediated apoptosis.