青心酮对ApoE(-/-)小鼠动脉粥样硬化斑块中巨噬细胞5-脂氧合酶的影响

Effects of 3,4-dihydroxyacetophenone on 5-lipoxygenase in Macrophages of Atherosclerosis Plaque

目的观察青心酮防治ApoE(-/-)小鼠主动脉粥样硬化病变(atherosclerosis,AS)与5-脂氧合酶的关系。方法传代培养小鼠巨噬细胞株RAW264.7,分成4组:正常对照组,模型组,青心酮组,辛伐他汀组。收集各组细胞蛋白,应用Western-blot检测5-脂氧合酶含量;收集上清液,用ELISA检测白三烯B4(leukotrieneB4,LTB4)。以C57BL/6小鼠作正常对照组,24只雄性ApoE(-/-)小鼠随机分成3组:模型组(等量乙醇),青心酮治疗组(20 mg·kg-1·d-)1,辛伐他汀治疗组(20 mg·kg-1·d-)1,给药8周。所有实验小鼠饲以普通饲料至16周。取血检测LTB4,剪取主动脉根部行组织切片,HE染色观察主动脉粥样硬化病变情况;剪取主动脉根部斑块组织,Western blot法测定斑块中5-脂氧合酶水平。结果青心酮处理后LTB4降低,5-脂氧合酶含量减少,AS病灶形成数目、面积减少。结论青心酮能减轻ApoE(-/-)小鼠动脉粥样硬化病变,可能与其抑制5-脂氧合酶,减少LTB4有关。

Objective To observe the effects of 3,4-dihydroxyacetophenone（DHAP） on 5-1ipoxygenase in macrophages （MC） of ApoE （-/-） atherosclerosis （AS） mice. Methods The subcuhured MC （RAW264.7 cell lines） were divided into four groups, normal control group, model group, DHAP group and Simvastatin group. The content of 5-1ipoxy- geuase in cell protein was detected with Western blot method, and leukotriene B4 was analyzed by ELISA. C57BL/6 mice served as the normal control group, and 24 male ApoE （-/-） mice were equally randomized into 3 groups, model group（ip., 2 mg·kg^-1·d^-1 of ethylalcohol）, DHAP group（ip., 20 mg·kg^-1·d^-1 of DHAP） , simvastatin treatment group （ip., 20 mg·kg^-1·d^-1 of simvastatin）. All mice were fed with a common diet for 16 weeks, and the medication lasted 8 weeks. TB4 in the blood was collected. Sections of aortic root were stained by HE, and the content of 5- lipoxygenase in atherosclerotic plaques at the aortic root was examined by Western blot. Results The concentration of LTB4 was decreased, the formation of AS plaque was reduced, 5-1ipoxygenase content at atherosclerosis plaque was also decreased, and the number and area of AS focus was reduced in DHAP- treated group. Conclusion It suggested that DHAP could be effective for the prevention and treatment of AS, and its possible mechanism is related with the inhibition of 5-1ipoxygenase and the decrease of TB4.