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

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(leukotriene B4,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.

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

Objective To observe the effects of 3,4-dihydroxyacetophenone(DHAP) on 5-lipoxygenase in macrophages(MC) of ApoE(-/-) atherosclerosis(AS) mice.Methods The subcultured MC(RAW264.7 cell lines) were divided into four groups,normal control group,model group,DHAP group and Simvastatin group.The content of 5-lipoxygenase 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-lipoxygenase 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-lipoxygenase and the decrease of TB4.