| Objective: To investigate the expressive change of PPARβin global cerebral ischemia/reperfusion rats, and the protective effect of PPARβon brain injury induced by global cerebral ischemia/reperfusionMethods: The model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion and haemospasia hypotension in rats. GW0742 (22μg, 67μg and 200μg), a selective PPARβagonist, was intracerebroventriclarlly administered 30 min before ischemia/reperfusion. Spatial learning and memory function of rat was determined by Morris water maze. Morphologic changes of hippocampal neurons were evaluated by HE staining. The PPARs mRNA and protein expression in rat hippocampi were detected by RT-PCR and western-blotting. The changes of SOD activity in rat hippocampi was measured by xanthinoxidase method. The change of MDA content in rat hippocampi was measured by the method of TBA. The concentrations of TNF-α, IL-1β, IL-6 and IL-10 in rat hippocampi were measured by ELISA. The changes of NF-κB p65 expression in rat hippocampi was detected by immunohistochemistry.Results: The spatial learning and memory function of global cerebral ischemia/reperfusion injury rat was significantly impaired compared with that of sham operation group. Hippocampal neurons in model rat showed obviously karyopycnosis. Compared with that of sham operation group , the PPARβmRNA and protein expression in hippocampi remarkably increased at 2 h , and reached the peak at 48 h after global cerebral ischemia/reperfusion. At 15 d, the level of PPARβmRNA and protein expression was still higher than that of sham operation group. But there was no significance of the PPARβmRNA and protein expression levels between the model group and sham operation group at 30 d.GW0742, a PPARβselective agonist, remarkably improved the spatial learning and memory function impairment, obviously prevented the hippocampal neurons from karyopycnosis and loss induced by global cerebral ischemia/reperfusion in rats. The administration of GW0742 significantly increased the SOD activity and decreased MDA content of global cerebral ischemia/reperfusion damage rat. GW0742 also remarkably blunted the increase of inflammatory factors NF-κB, TNF-α, IL-1β, and IL-6, and the decrease of IL-10. GW0742 remarkably down-regulated PPARβmRNA and protein expression in hippocampi of global cerebral ischemia/reperfusion damage rats.Conclusions: Global cerebral ischemia/reperfusion can induce the learning and memory function disorder of rats and the PPARβmRNA and protein expression increase. GW0742 has an obviously neuroprotective effect on global cerebral ischemia/reperfusion injury in rats. The action of antiinflammation and antioxidative stress of GW0742 may be involved in the protective mechanism. |
