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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 arachidonate 5-lipoxygenase (5-LO) pathway in atherosclerosis in ApoE - / - mice. Methods 24 ApoE - / - male mice aged 8 weeks [body weight (22.42 ± 1.21) g] were randomly divided into 2 groups: control group (n = 12, normal feed), arteriosclerosis model group High-fat feed). The plaque area (PA / LA) was corrected by pathological analysis after 16 weeks. The expression of 5-LO in the aorta was detected by RT-PCR and Western blot. The levels of leukotriene B4 (LTB4) and Serum levels of leukotriene D4, LTD4. Results The model was successfully established, and atherosclerotic plaque was formed in atherosclerotic model group. The expression of 5-LO mRNA in the aorta in atherosclerosis model group was significantly higher than that in the control group [(0.61 ± 0.0) vs (0.18 ± 0.03), P <0.01] and the protein expression [(1.53 ± 0.18) vs (0.52 ± 0.40 ), P <0.01], the level of LTB4 in serum [(34.79 ± 4.47) vs (12.07 ± 2.35), P <0.01] and LTD4 level [(2 862.48 ± 48.77) vs (357.10 ± 53.57) 0.01] significantly increased. The levels of LTB4 (r = 0.954, P <0.01) and LTD4 (r = 0.946, P <0.01) in the model of atherosclerosis were positively correlated with the corrected plaque area. Conclusion 5-lipoxygenase pathway plays an important role in the pathogenesis of atherosclerosis.