5-脂氧化酶转基因小鼠表型初步研究  

A Preliminary Study on Phenotype of 5-Lipoxygenase Transgenic Mice

作　　者：张梅英[1] 杨葳[1] 吴红联[1,2] 董婉维[1] 周生来[1] 于洋[1] 王惟[1] 郭晓冲[1] 郑志红[1] 

机构地区：[1]中国医科大学实验动物学部,沈阳110001 [2]北京大学实验动物中心,北京100871

出　　处：《实验动物与比较医学》2015年第4期265-270,共6页Laboratory Animal and Comparative Medicine

基　　金：辽宁省高校科研项目计划（2008S239）;辽宁省科技计划项目（2008408002-2,2014408001）

摘　　要：目的建立5-脂氧化酶（5-LO）高表达转基因小鼠模型，为动脉粥样硬化（AS）发病分子机制的研究提供有应用价值的动物模型。方法对5-LO转基因及正常对照小鼠分别选用RT—PCR、免疫组织化学、血脂、血压监测等方法进行分析实验。结果5-LO及大鼠5-脂氧合酶激活蛋白（FLAP）免疫组织化学实验结果显示，在肾和肺中5-LO及FLAP的表达，转基因小鼠高于正常对照组小鼠：RT—PCR实验结果显示，转基因小鼠与正常对照小鼠比较在骨髓细胞、腹腔细胞、脾脏、肾脏中白三烯介质及其受体均有不同程度的高表达。其中，两种小鼠的腹腔细胞和骨髓细胞中白三烯A4（LTA4）、白三烯B4（LTB4）和半胱酰胺-白三烯受体2（Cys—LTR2）的表达存在差异（P〈0．05），脾和肾脏中LTB4、白三烯C4（LTC4）及Cys—LTR2的表达存在差异（P〈0．05），肾脏中半胱酰胺-白三烯受体1（Cys-LTR1）的表达存在差异（P〈0．05）。C反应蛋白（CRP）、白介素-1β（IL-1β）、血小板衍生因子（PDGF）、坏死因子-κB（NF-κB）等细胞因子检测结果显示，在肾组织中转基因小鼠的各项指标显著高于正常对照小鼠（P〈0．05）；血压测定结果显示，转基因小鼠高于正常对照小鼠（P〈0．05）；血脂检测结果显示，两种小鼠未见明显差异（P〉0．05）。结论成功建立5-LO高表达转基因小鼠模型。Objective To establishment a 5-1ipoxygenase （5-LO） transgenic mouse model, which may be used for the research of the pathogenesis of atherosclerosis. Methods RT-PCR and immunohistichemistry was used to detect 5-LO transgenic mice and control mice. The cholesterol and blood pressure was also detected. Result Expression of 5-LO and 5-1ipoxygenase activating protein （LFAP） were higher in the kidney and lung of the 5-LO transgenic mice than the control mice. The results of RT-PCR showed that the expression of leukotriene and its receptor were higher in the bone marrow cells, peritoneal cells, spleen and kidney of the 5-LO transgenic mice than the control mice. Compared the 5-LO transgenic mice with the control mice, there were significant differences in the expression of LTA4, LTB4 and Cys-LTR2 in the bone marrow cells and peritoneal ceils （P〈0.05）, there were signifi- cant differences in the expression of LTB4, LTC4 and Cys-LTR2 in the spleen and kidney （P〈0.05）, there was a significant difference in the expression of Cys-LTR1 in the kidney （P〈0.05）, there were significant differences in the expression of CRP, IL-1β, PDGF and NF-κB in the kidney （P〈0.05）. The result of blood pressure determination showed that it was higher in the 5-LO transgenic mice than the control mice （P〈0.05）, and there was no significance in the cholesterol （P〉0.05）. Conclusion The 5- LO transgenic mouse model has been established.

关 键 词：5-脂氧化酶(5-LO) 动脉粥样硬化(AS) 转基因小鼠 

分 类 号：R543.5[医药卫生—心血管疾病] R-332[医药卫生—内科学]