Vinpocetine alleviates cerebral ischemia-reperfusion injury in rats by regulation of the expressions of nuclear factor кB p65, peroxisome proliferator-activated receptor γ and cyclooxygenase-2

Abstract

Objective To investigate neuroprotective mechanisms of vinpocetine by observing the effects of vinpocetine injection on the expressions of peroxisome proliferators-activated receptor γ (PPARγ), nuclear factor (NF)-кB p65, cyclooxygenase-2 (COX-2) in the ischemic cortex, and infarct volume after focal cerebral ischemia-reperfusion in rats. Methods A focal cerebral ischemia-reperfusion injury model was induced by suture method. The rats were randomly divided into a normal control, a cerebral ischemia-reperfusion and a vinpocetine groups. They were also divided into either a day 7 subgroup or a day 14 subgroup (n=6 in each subgroup) according to the reperfusion time. Western blot was used to detect the expression levels of PPARγ and NF-κB P65 in the ischemic cortex. Triphenyl tetrazolium staining was used to detect the volume of cerebral infarction. Results Western blot showed that at day 7 and 14 after cerebral ischemia-reperfusion, expression levels of PPARγ (all P<0.001) and NF-κB p65 (all P<0.001) in the cerebral ischemia-reperfusion group were significantly higher than those in the sham operation group, the expression levels of PPARγ (all P<0.05) in the vinpocetine group were significantly higher than those in the cerebral ischemia-reperfusion group, but the expression levels of NF-κB p65 (all P<0.05) were significantly lower than those in the cerebral ischemia-reperfusion group. Reverse transcription polymerase chain reaction showed that COX-2 mRNA expression levels were upregulated significantly at day 7 and 14 after cerebral ischemia-reperfusion compared with the sham operation group (all P<0.001), the expression levels of COX-2 mRNA in the vinpocetine group were significantly downregulated compared with the cerebral ischemia-reperfusion group (all P<0.05). The infarct volumes at day 7 (134.308±9.954 mm3vs. 185.543±9.100 mm3;q=10.659, P<0.001) and at day 14 (137.865±9.094 mm3vs. 183.210±4.368 mm3;q=11.166, P<0.001) in the vinpocetine group were significantly less than those in the cerebral ischemia-reperfusion group. Conclusions Vinpocetine significantly reduces infarct volume after focal cerebral ischemia-reperfusion, its mechanism may be associated with upregulation of PPARγ expression and downregulation of the expressions of NF-κB p65 and COX-2. Key words: Brain Ischemia; Reperfusion Injury; Vinca Alkaloids; NF-κB; PPAR γ; Cyclooxygenase 2; Neuroprotective Agents; Rats