Neuroprotective Effects Of Fenofibrat On SD Rats With Focal Cerebral Ischemia Reperfusion Injury And Its Mechanism

ObjectiveTo investigate the influence of fenofibrate,a peroxisome proliferator-activated receptor α (PPARα) agonists on the expression of tumor necrosisfactor-α(TNF-α), interleukin-1β (IL-1β) and nuclear transcription factor-kB (NF-κB) in brain tissue of rats with focal cerebral ischemia reperfusion injury. Toobjective its neuroprotective effects of Fenofibrate on rats with focal cerebralischemia reperfusion injury and related mechanisms. And to explore theintervention time preliminary.Methods128healthy male SD rats were randomly divided into normal group, shamoperation group, cerebral ischemia reperfusion group (model group), fenofibratetreatment groups, according intervention time point treatment group was dividedinto5subgroups:2h before ischemia, simultaneous administration,2h,4h,6hafter ischemia. A rat model of cerebral ischemia reperfusion was establishedaccording to modified intraluminal suture method of Zea Longa. Rats infenofibrate treatment groups were respectively given fenofibrate (300mg/Kg)through Irrigation stomach in the time of2hours before ischemia, ischemia,2h,4h,6h after ischemia. Fenofibrate is soluble in0.5g/L sodium carboxy methylcellulose and the same amount of menstruum was given sham operation groupand ischemia-reperfusion group. The neurological deficit of rats were evaluatedaccording to Longa’s method. HE stained, to observe pathological changes of the hippocampal CA1region.To objective the expression of NF-κB, TNF–α andIL-1β protein in the region of hippocampal CA1by immunohistochemical stained.To determine the content of TNF-α and IL-1β protein in hippocampal CA1regionby enzyme-linked immunosorbent assay.Results1. The neurological deficit score: There was no neurological deficit in thesham-operated group, and rats in model group and fenofibrate treatment groupshowed significant neurological deficit. Compared with model group, neurologicaldeficit in2h before ischemia, simultaneous administration,2h after ischemia intreatment group was significant improvement, and there was statistically significantdifferences (P <0.05). Compared with cerebral ischemia group, there were nosignificant difference (P>0.05) in after ischemia4h and6h administration rats.2. HE stained: In sham operation group, in regin of hippocampal CA1cellmorphology in neurons was normal, boundary and clear nucleoli, closelyarranged, neat. Oppositely in model group and treatment group: nerve cells werearrangeddisordered, enlarged in varying degrees, nucleolar enriched, fragment-ed, disappeared.3. Compared with the sham group, NF-κB, TNF-α, IL-1β protein expressionin region of hippocampal CA1in model group and treatment group weresignificantly higher (P <0.01) by immunohistochemical stained. And TNF-α andIL-1β protein content were significantly higher (P<0.01) than sham groupthrough ELISA. Compared with model group,2h before ischemia, in the time ofischemia,2h after ischemia in treatment group, the above indexes weresignificantly reduced (P <0.05).4h,6h after ischemia in treatment groupe theabove indesxes were no significantly changes (P>0.05).ConclusionsPPARα agonist fenofibrate has significant neuroprotective effects oncerebral ischemia-reperfusion injury, and its mechanism may be with the inhibition of NF-κB activation, reducing the inflammation factors of TNF-α, IL-1βgeneration, and the best effects were early administration in brain ischemia.