Effects of fenofibrate on global cerebral ischemia/reperfusion injury in rats / 中国药理学通报

ABSTRACT

Aim To investigate the effect of fenofibrate on focal 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, 100, 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.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 biochemistry, and IL-1β, IL-6, IL-10, TNF-α levels were detected by ELISA.Results Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and losing induced by I/R. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1β, IL-6, and the decrease of IL-10 and SOD activities of I/R rats.Conclusions Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activating PPARα.The anti-inflammation and antioxidative stress of fenofibrate may be involved in the protective mechanism.