The Relationship Between 5-LO Expression And Cerebral Damage In Global Cerebral Ischemia Reperfusion Rats

Aim: To primarily explore the relationship between 5-1ipoxygenase (5-LO) expression and cerebral damage in global cerebral ischemia reperfusion (I/R) rats.Methods:(1)The rat model of global cerebral ischemia reperfusion was prepared by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension. To observe the change of 5-LO mRNA and protein expression respectively after I/R 30min,2h,6h,24h,48h,7d,15d and 30d. Caffeic acid (10mg·kg-1, 30 mg·kg-1 and 50 mg·kg-1) was intragastriclly administered 30 min before the operation in I/R 7d rats.(2)Morris water maze was used to evaluate the ability of spatial learning and memory function of rat.HE staining was used to observe pathomorphological changes and neurons number of hippocampal. Expression of 5-LO mRNA and protein in rats hippocampus was evaluated with RT-PCR and Western blot, respectively. NF-κBp65 expression was detected by the methods of immunohistochemistry. SOD activities and MDA contents were analyzed by the methods of biochemistry.Results: Compared with that of sham operated group,the spatial learning and memory function of rats in global cerebral ischemia reperfusion group was significantly impaired,and hippocampal neurons showed obviously karyopycnosis and loss.SOD activity significantly decreased and MDA content significantly increased in rat hippocampus. The increase of NF-KBp65 expression was significantly blunted. The 5-LO mRNA and protein expression in hippocampus increased remarkably at 24h and 48h after global cerebral ischemia reperfusion,and reached the peak at 7d.The level of 5-LO mRNA expression was still higher than that of sham operated group,and there was significance between model group and sham operated group at 15d and 30d.Caffeic acid can remarkably shorten the exploring time of rat and obviously relieved the karyopycnosis and injury in hippocampus neurons induced by global cerebral ischemia reperfusion. Caffeic acid significantly blunted the increase of 5-LO mRNA and protein expressions in rat hippocampus of global cerebral ischemia reperfusion. Caffeic acid significantly blunted the increase of NF-KBp65 expression and MDA content, increase the SOD activities in rats induced by global cerebral ischemia reperfusion. Caffeic acid significantly blunted the increase of 5-LO mRNA and protein expressions in hippocampus of I/R rats.Conclusions: 5-LO expression involves in the brain injury process and the inhibitor of 5-LO will be a candidate drug which can prevente the rats from cerebral damage induced by global cerebral ischemia reperfusion.