Effect And Mechanism Of PPARγ Expression And Activation On Brain Damage Induced By Ischemia Reperfusion In Rats

Objective:To explore the protective effect and mechanism of PPARγexpression and activation on brain damage induced by ischemia/reperfusion in rats.Methods:The rat model of global brain ischemia/reperfusion (I/R) injury was established by bilateral common carotid arteries occlusion and cervicalis vena retransfusion. Morris water maze was used to assess the change of spatial learning and memory functions, HE staining was used for evaluation of pathohistological changes of hippocampal neurons, RT-PCR and Western blotting was performed to detect the expression change of PPARγmRNA and protein. ELISA and immunohistochemistry staining was used to measured the content of IL-1, IL-6, IL-10 and TNF-α,and the NF-κB expression. The SOD activity and MDA content were also detected. Rosiglitazone (0.8 mg/kg, 2.4 mg/kg and 7.2 mg/kg), a selective PPARγ, agonist, was injected intraperitoneally at 1 h before I/R. GW9662(5ug), a selective PPARγantagonist, was intraventricularlly injected at 0.5 h before rosiglitazone administration.Results: The spatial learning and memory ability of model rats was significantly impaired. In model rats, hippocampal neurons showed obvious karyopycnosis and loss. The PPARγmRNA and protein expression in hippocampus significantly increased after global cerebral I/R in rat, arrived at the peak at 48 h, and nearly closed to normal lever in 30 d after I/R.The administration of rosiglitazone ameliorated the learning and memory function impairment, prevented hippocampal neurons from damage, and down regulated the happocampal nouronal PPARγmRNA and protein expression induced by I/R in rats. Rosiglitazone significantly blunted the increase of MDA, IL-1, IL-6 and TNF-αcontent and NF-κB expression, and the decrease of SOD activity induced by I/R in rats. However, the dose-dependent protective action of rosiglitazone was canceled by pretreatment of GW9662. Neither Rosiglitazone nor GW9662 has obvious effect on PPARα, PPARβmRNA and protein expression.Conclusions:PPARγexpression and activation can protect rat brain from damage by I/R. The protective mechanism may be involved in its inhibition of inflammatory reaction and oxidative stress in CNS.