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Probucol and atorvastatin in combination protect rat brains in MCAO model:Upregulating Peroxiredoxin2,Foxo3a and Nrf2 expression

杜媛媛  张祥建  季辉  刘海超  李姝雅  李利涛  
【摘要】:Background and object;Inflammation and oxidative stress play an important role in cerebral ischemic pathogenesis.It has been well established that atorvastatin and probucol could elicit a variety of biological effects through its antiinflammatory and anti-oxidant properties respectively.This study was to examine whether probucol and atorvastatin in combination had the enhanced protective effect against cerebral ischemia.Methods-.Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion(MCAO).Experiment 1 was used to evaluate the time course expression of Peroxiredoxin2(Prx2)and Foxo3 a after cerebral ischemia.Experiment 2 was used to detect neuroprotective effect of atorvastatin and probucol in cerebral ischemia.At 24 h or 72 h,neurologic deficit,brain water content and infarct size were measured.Immunohistochemistry,RT-PCR,Western blot and confocal microscope were used to analyze the expressions of Prx2,Foxo3 a and nuclear factor erythroid 2-related factor 2(Nrf2).Compared with the normal-control group,the expressions of Prx2 and Foxo3 a were down-regulated in ischemic brain.Results;Compared with the use of probucol or atorvastatin alone,the combined treatment dramatically reduced the brain water content and the infarct volume(P 0.05).Meanwhile,the decrease of Prx2,Foxo3 a and Nrf2 was significantly alleviated in combined treatment group.Conclusion;Probucol combined with atorvastatin can get the augmented neuroprotection from the damage caused by MCAO,this effect may be through up-regulation of Prx2,Foxo3 a and Nrf2.

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