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Neuroprotective effect of luteolin-7-O-β-D-glucuronide in a rat model offocal cerebral ischemia

作者:Sheng-qun; HOU; Jia-ying; YE; Hai-feng...

摘要:OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute.olin-7-O-β-D-glucuronide(LGU) against focalcerebral ischemic injury.METHODS The focal cerebral ischemic injury model was established by middle cerebral artery occlusion(MCAO).Male Sprague Dawley rats were randomly divided into sham group,model group(MCAO),LGU group(0.24,0.72 and2.16 mg·kg-1) and positive control group(Edaravone at 5 mg·kg-1).LGU was injected intravenously 30 min after MCAO.Neurological severity score,infarct volume and brain water content were detected 24 h after MCAO and the levels of Na+-K+ ATPase,Ca2 + ATPase,TNF-α and IL-1β were detected to explore the possible mechanisms.For the therapeutic time window test,LGU(0.72 mg·kg-1) was injected intrave.nously 0.5,2,4,6,8,10 and 12 h respectively after MCAO.To evaluate motion behavior,LGU were injected intravenously 30 min after MCAO and once per day during detection period.The changes of motor coordination were detected by rotating rod method and grip strength analysis,and the changes of gaits were detected using DigiGait Imaging System.RESULTS LGU improved the neurological severity score,infarct volume ratio and brain water content.The therapeutic time window of LGU for cerebral infarction and brain edema was at least 6 h and for neurological dysfunction was 12 h.LGU also prolonged the latency on rotarod,increased the forelimb tension and improved 8 gait parameters,including stance duration,stride length,stance width,paw area,paw area variability,gait symmetry,ataxia coefficient and tau propulsion.Furthermore,LGU increased Na+-K+-ATPase and Ca2+-ATPase levels in the cortex and hippocampus in the ischemic side,reduced the levels of TNF-α and IL-1β in the serum.CONCLUSION LGU has a significant neuroprotective effect against cerebral ischemic injury via improving energy metabolism and reducing inflammation.

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