Effect of flurbiprofen postconditioning on permeability of blood brain barrier in a rat model of focal cerebral ischemia-reperfusion injury / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of flurbiprofen postconditioning on the permeability of blood brain barrier in a rat model of focal cerebral ischemia-reperfusion (I/R) injury.Methods:Eighty healthy male Wistar rats, aged 8-9 weeks, weighing 280-320 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group Sham), focal cerebral I/R group (group I/R), lipo-microballoons group (group V) and flurbiprofen 10 mg/kg group (group F). Focal cerebral I/R model was established by left middle cerebral artery occlusion for 2 h followed by 24-h reperfusion in anesthetized rats.Flurbiprofen 10 mg/kg (group F), the equal volume of lipo-microballoons (group V) or the equal volume of normal saline (group Sham and group I/R) was injected via the tail vein at the onset of reperfusion.The rats were sacrificed at 24 h of reperfusion, brains were immediately removed, and cerebral tissues were obtained for measurement of brain water content, Evans blue content, expression of matrix metalloproteinase-9 (MMP-9) in ischemic penumbra (by immuno-histochemistry), and expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and inducible nitric oxide synthase (iNOS) in ischemic penumbra (by Western blot). Results:Compared with Sham group, brain water content and Evans blue content in brain tissues were significantly increased, and the expression of MMP-9, p-p38 MAPK and iNOS in ischemic penumbra was up-regulated in I/R, V and F groups ( P<0.05). Compared with group I/R, brain water content and Evans blue content in brain tissues were significantly decreased, and the expression of MMP-9, p-p38 MAPK and iNOS in ischemic penumbra was down-regulated in group F ( P<0.05), and no significant change was found in the above parameters in group V ( P>0.05). Conclusion:Flurbiprofen postconditioning can decrease the permeability of blood brain barrier during focal cerebral I/R in rats, and the mechanism may be related to inhibiting the activation of p38 MAPK/iNOS signaling pathway and down-regulating the expression of MMP-9.