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

Abstract 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 anti-inflammatory and anti-oxidant properties respectively. This study was to examine whether probucol and atorvastatin in combination had the enhanced protective effect against cerebral ischemia. 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 Foxo3a 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, Foxo3a and nuclear factor erythroid 2-related factor 2 (Nrf2). Compared with the normal-control group, the expressions of Prx2 and Foxo3a were down-regulated in ischemic brain. Compared with the use of probucol or atorvastatin alone, the combined treatment dramatically reduced the brain water content and the infarct volume ( P