3-n-Butylphthalide (NBP) reduces apoptosis and enhances vascular endothelial growth factor (VEGF) up-regulation in diabetic rats.
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/mm(2) in diabetic rats versus 320.6 +/- 21.9 cells/mm(2) in control rats, p<0.05, n=5) and VEGF(+)-caspase-3(+) (393.4 +/- 24.2 cells/mm(2) versus 135.8 +/- 12.0 cells/mm(2) 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/mm(2), n=5), while the caspase-3 expression was reduced (240.0 +/- 15.1 cells/mm(2), n=5) in the NBP-treated diabetes mellitus-NBP rats.


CONCLUSIONS
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.
Zhang
Ting
T
Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Jia
Weiping
W
Sun
Xiaojiang
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D001572:Benzofurans; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C027125:3-n-butylphthalide