5-脂氧合酶通路在ApoE基因敲除小鼠动脉硬化中的作用  

Role of 5-lipoxygenase pathway in atherosclerosis in ApoE knockout mice

作　　者：衡旭华[1] 杨丽霞[1] 郭瑞威[1] 石燕昆[1] 杨智华[1] 

机构地区：[1]成都军区昆明总医院心血管内科,昆明650032

出　　处：《第三军医大学学报》2012年第13期1310-1313,共4页Journal of Third Military Medical University

基　　金：成都军区"十一五"计划课题(MA07010)~~

摘　　要：目的探讨5-脂氧合酶(arachidonate 5-Lipoxygenase,5-LO)通路在ApoE-/-小鼠动脉硬化中的作用。方法将8周龄ApoE-/-雄性小鼠24只[体质量(22.42±1.21)g]随机分为2组:对照组(n=12,普通饲料)、动脉硬化模型组(n=12,高脂饲料)。16周后,病理检测分析校正斑块面积(PA/LA);RT-PCR和Western blot法检测主动脉中5-LO的表达;酶联免疫法检测白三烯B4(leukotriene B4,LTB4)和白三烯D4(leukotriene D4,LTD4)的血清水平。结果建模成功,动脉硬化模型组粥样斑块形成。动脉硬化模型组较对照组小鼠主动脉中5-LO的mRNA的表达[(0.61±0.0)vs(0.18±0.03),P<0.01]及蛋白表达[(1.53±0.18)vs(0.52±0.40),P<0.01]明显升高,血清LTB4水平[(34.79±4.47)vs(12.07±2.35),P<0.01]及LTD4水平[(2 862.48±48.77)vs(2 357.10±53.57),P<0.01]显著升高。动脉硬化模型组血清LTB4(r=0.954,P<0.01)、LTD4(r=0.946,P<0.01)水平与校正斑块面积成正相关。结论 5-脂氧合酶通路在动脉粥样硬化发病机制中起着重要作用。Objective To investigate the role of the 5-lipoxygenase pathway in atherosclerosis of ApoE knockout mice. Methods Twenty-four 8-week-old male ApoE ＋ mice with body weight of 22.42± 1.21 g were randomized into control group （n = 12, normal diet） and atherosclerotic model group （n = 12, high fat diet）. After 16 weeks＇ feeding, all animals were sacrificed. The corrected plaque areas （PA/LA） of the aortic were measured. The expression of 5-1ipoxygenase at gene and protein levels in aorta were detected separately through RT-PCR and Western blotting. Serum levels of leukotriene B4 （ LTB4 ） and leukotriene ]）4 （LTD4） were measured by ELISA. Results Atheromatous plaques were found in the atherosclerotic model group, indicating the successful establishment of the model. The expression of 5-LO at mRNA （0.61 ± 0.05 ） and protein （ 1.53 ±0.18） levels in the aorta of atherosclerosis model group were obviously higher than those in the control group （0.18 ± 0.03 and 0.52 ±0.40, P 〈 0.01 ）. So were the serum levels of LTB4 （34.79 ± 4.47 vs 12.07 ±2.35, P 〈0.01 ） and LTD4 （2 862.48 ±48.77 vs 2 357.10 ±53.57, P 〈0.01 ）. The serum levels of LTB4 and LTD4 were positively correlated with the corrected plaque areas （r = 0. 954, P 〈 0.01, and r = 0. 946, P 〈 0.01 ）. Conclusion The 5-1ipoxygenase pathway may play a significant role in the pathogen- esis of atherosclerosis in ApoE knockout mice.

关 键 词：5-脂氧合酶 动脉粥样硬化 白三烯B4 白三烯D4 

分 类 号：R329.26[医药卫生—人体解剖和组织胚胎学] R363.21[医药卫生—基础医学]