动脉粥样硬化斑块内FIZZ1表达促进平滑肌细胞清道夫受体-A上调

目的探讨ApoE基因敲除鼠动脉粥样硬化斑块内FIZZ1表达情况及其对平滑肌细胞清道夫受体A(SR-A)表达的影响.方法C57BL/6J ApoE基因敲除鼠及C57BL/6J野生型小鼠各9只,分别喂养高脂饲料及普通饲料,24周后处死小鼠,石蜡包埋血管后做连续切片,行HE染色及FIZZ1免疫组化.用氧化型低密度脂蛋白(ox-LDL)以及终浓度分别为3×10-6mmol/L、9×10-6mmol/L、2.7×10-5mmol/L的FIZZ1刺激培养的平滑肌细胞,激光共聚焦显微镜确认SR-A表达后,流式细胞术检测FIZZ1对ox-LDL诱导的平滑肌细胞SR-A表达的影响.结果ApoE基因敲除鼠高脂饲养24周后,主动脉根部明显形成动脉粥样硬化,可见FIZZ1在动脉粥样硬化斑块内明显表达,同龄野生型C57BL/6J鼠正常血管壁内,未见FIZZ1表达,重组FIZZ1能明显促进ox-LDL诱导的平滑肌细胞SR-A表达(与对照组比较,P<0.01).结论C57BL/6J野生型小鼠正常血管不表达FIZZ1,C57BL/6JApoE基因敲除鼠动脉粥样斑块表达FIZZ1,FIZZ1促进ox-LDL诱导的平滑肌细胞SR-A表达,提示FIZZ1可能在ApoE基因敲除鼠动脉粥样硬化进展中起一定的促进作用.

The expression of FIZZ1 in atherosclerotic plaque of ApoE-/- mouse promotes SR-A expression in vascular smooth muscle cells

Objective To explore the expression of FIZZ1 in atherosclerotic plaque of ApoE-/mouse and the effect of FIZZ1 on Scavenger receptor A(SR-A) expression in vascular smooth muscle cells(VSMCs).Methods Nine C57BL/6J ApoE-/-mice fed with high fat diet and 9 C57BL/6J mice fed with normal diet were investigated.24 weeks later,all the mice were euthanized and aortas were collected.HE staining and FIZZ1 immunohistochemistry were performed on the aortic tissue after paraffin embedding.VSMCs were treated with ox-LDL(20mg/L) plus recombinante FIZZ1 at different final concentration(3×10-6mmol/L,9×10-6mmol/L,2.7×10-5mmol/L).SR-A expression in VSMCs was detected by flow cytometry and laser confocal microscopy.Results After 24 weeks of high fat diet treatment,large atherosclerotic plaque was found formed at ApoE-/-mouse aortic root.FIZZ1 was found in atherosclerotic plaque of ApoE-/-mice by immunohistochemistry.Recombinant FIZZ1 enhanced ox-LDL induced SR-A expression in VSMCs(FIZZ1 groups vs.control group,all P<0.01). Conclusions FIZZ1 was found in atherosclerotic plaque of C57BL/6J ApoE-/-mice while no FIZZ1 was expressed in normal aorta of C57BL/6J wild type mice.Recombinant FIZZ1 enhanced ox-LDL induced SR-A expression in VSMCs,which indicates the involvement of FIZZ1 in the development of atherosclerosis in C57BL/6J ApoE/-mice.