Protective Effect of Dipfluzine on Focal Cerebral ischemia-reperfusion Injury

AIM To compare the protective effects of dipfluzine (Dip) and flunarizine (Flu) on the focal cerebral ischemia-reperfusion injury in rats. METHODS Endothelin-1(ET-1) was perfused to the proximity of the middle cerebral artery (MCA) to induce focal cerebral ischemia-reperfusion model. Solvent, Dip 10, 20 and 40mg•kg^(-1) and Flu 20mg•kg^(-1) were given ip 30min and 4.5h after ET-1 perfusion. The changes in cerebral blood flow (CBF) in striatum before and after ET-1 perfusion were characterized using hydrogen clearance technique. The infarct volume, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum were measured respectively at 24h after ET- 1 application to evaluate the effects of Dip and Flu. RESULTS Dip 20 and 40mg•kg^(-1) significantly alleviated the CBF decrease at 70 and 100min after ET-1 perfusion, but Dip 10mg•kg^(-1) did not. Flu 20mg•kg^(-1) could enhance CBF only at 100min, which showed relative weak effect on CBF. A significant reductions in infarct volume were found in Dip-treated groups as well as in Flu-treated group compared with the solvent group, and Dip showed a dose-dependent reduction (r=0.9797, P＜0.01). Furthermore, Dip and Flu also raised SOD activity and decreased MDA content in serum. CONCLUSION Dip and Flu showed significant protective effects against cerebral ischemia-reperfusion injury via increasing CBF in ischemic-regions and their antioxidant activity. Dip showed a relatively stronger effect than Flu in improving CBF.