5-脂氧合酶通路在ApoE基因敲除小鼠动脉硬化中的作用

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。

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

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-lipoxygenase at gene and protein levels in aorta were detected separately through RT-PCR and Western blotting.Serum levels of leukotriene B4(LTB4) and leukotriene D4(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-lipoxygenase pathway may play a significant role in the pathogenesis of atherosclerosis in ApoE knockout mice.