甲酯化脂氧素A4对局灶性脑缺血再灌注损伤的保护作用及其机制研究-麻醉学专业论文.docxVIP

华中科技大学博士学位论文 华 中 科 技 大 学 博 士 学 位 论 文 PAGE 6 PAGE 6 Protective Effects and Mechanisms of Lipoxin A4 Methyl Ester on Transient Cerebral Ischemia and Reperfusion Injury Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology Doctoral candidate : Ye Xihong Supervisor : Prof. Yao Shanglong Abstract PartⅠ Effect of lipoxin A4 methyl ester on cerebral ischemia reperfusion injury in rats Objective To establish intraluminal suture right middle cerebral artery occlusion (MCAO) model and investigate effects of lipoxin A4 methyl ester (LXA4 ME) on cerebral ischemia reperfusion injury in rats. Methods Fourty-eight adult male Sprague-Dawley rats were divided randomly into four groups: sham-operated group (sham group), ischemia/reperfusion group (I/R group), low dose of LXA4 ME group (0.03 nM LXA4 ME，L group) and high dose of LXA4 ME group (0.3 nM LXA4 ME, H group). Rats were subjected to middle cerebral artery occlusion for 2 h. The neurological deficits, infarct volume and morphologic injury were assessed at 24 h after reperfusion. The myeloperxidase activity and the lipid peroxidation levels were evaluated. The concentration of IL-1β and TNF-α were studied by ELISA assay. Results Compared with sham group, LXA4 ME, especially at high dose, reduced infarct volume, improved neurological recovery, decreased numbers of neutrophil and suppressed malondialdehyde levels at 24 h after reperfusion. Also concentration of IL-1β and TNF-α in LXA4 ME groups was lower significantly. Conclusion Intraluminal suture MCAO model in rats provided reproducible MCA territory infarctions and allowed reperfusion by retracting the suture. LXA4 ME may be a promising neuroprotective approach to against focal cerebral ischemia reperfusion injury. Keywords Ischemia reperfusion, inflammation, brain, lipoxin A4, cytokines PartⅡ Lipoxin A4 methyl ester protects brain and reduces inflammation in a rat model of fo