| Aim: To investigate the effect of fenofibrate on global cerebral ischemia injury in rats and its mechanism.Methods: The rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension. Fenofibrate (33 mg·kg-1, 100 mg·kg-1 and 300 mg·kg-1) was intragastriclly administered 30 min before the operation, MK886 (6 mg·kg-1) was given intraperitoneally 30 min before administration of fenofibrate (300 mg·kg-1). Morris water maze was used to evaluate the ability of spatial learning and memory function of rats. HE staining was used to observe pathological morphological changes of hippocampal neurons. NF-κBp65 expression was detected by immunohistochemistry. SOD activities and MDA contents were analyzed by the methods of biochemistry. IL-1β, IL-6, IL-10 and TNF-αlevels were detected by the methods of ELISA. PPARα, PPARβand PPARγmRNA and proteins level in hippocampal neurons were measured using the methods of Reverse transcription-polymerase chain reaction (RT-PCR) and Western-Blot, respectively.Results: Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and lose induced by I/R in rats. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1βand IL-6 content, and the decrease of IL-10 content and SOD activity in I/R rats; the expressions of PPARαmRNA and protein were significantly down-regulated in hippocampus of I/R rats by fenofibrate. These effects of fenofibrate could be abolished by the pre-administration of MK886. However, fenofibrate had no significant effect on mRNA and protein expression of PPARβand PPARγin I/R rat hippocampus.Conclusions: Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activing PPARα. The anti-inflammation and antioxidative stress effects of fenofibrate maybe involved in its protective mechanism. |
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