Neuroprotective Effects Stuty On Cerebral Ischemia Reperfusion Injury Of Pioglitazone In Rats

Objective:To investigate the effect of the peroxisome proliferator-activated receptor-y(PPAR-y) activator pioglitazone on focal cerebral ischemia-reperfusion injury in rats and its corresponding mechanisms.Methods:A rat model of acute middle cerebral artery occlusion(MCAO) and reperfusion was established by suture embolism, eighty Sprague-Dawley rats were randomly(random number) divided into five groups as sham-operation group (group A), ischemia-reperfusion group (group B), pioglitazone group (group C), pioglitazone+GW9662group (group D) and DMSO group (group E), with24rats in each group. Relevant treatment were given to rats3days before focal cerebral ischemia operation respectively. After120min MCAO following24h of reperfusion, behavior scores of rats neuralogical fanction were penformed for each group; brain water content of the ischemic areal in8rats were randomly chosen from every group; enzyme-linked immunosorbent assay (ELISA) was respectively used to detect levels of NF-κB p65and IFN-y in cerebral tissue in8rats were randomly chosen from every group again; H·E staining is rsed to observe morphologic changes of neuron cells in ischemia/reperfusion injury region, Nissl and TUNEL staining were used to detect neuron apoptosis of all other rats in each group.Results:Compared with rats of group A, the score of neurological function、 brain water content、 the tissue levels of NF-κB p65and IFN-y and the ratio of neurocytes apoptosis in the other four groups were significantly increased(P<0.05); Compared with rats of group B, the score of neurological function、 brain water content、 the tissue levels of NF-κB p65and IFN-y and the ratio of neurocytes apoptosis in group C were significantly decreased(P<0.05), and the tissue levels of IFN-y and NF-κB p65in group B and group C were a perfect positive correlation(P<0.001); otherwise there was no difference between group B and group D and E about the correlation parameters. Compared with rats of group C, the score of neurological function、brain water content、the tissue levels of NF-κB p65and IFN-y and the ratio of neurocytes apoptosis in group D and E were significantly increased(P<0.05).Conclusion:The activator of PPAR-y (pioglitazone) in brain is probably through the route of PPAR-y to down-regulating NF-κB p65levels and then to reduce the release of pro-inflammatory mediators(IFN-y), alleviate organism inflammatory response, reducing the cellular edema and the change of cerebral ischemia-reperfusion injury, to protect neural function in rat and can then provide protection of neurocytes.