细颗粒物对Apo E基因敲除小鼠动脉粥样硬化斑块及其内部巨噬细胞表型的影响  

Effects of fine particulate matter(PM 2.5)on atherosclerotic plaque and macrophage phenotype in Apo E knockout mice

作　　者：李永辉[1] 崔佳[2] 赵培[2] 路永刚[2] LI Yonghui;CUI Jia;ZHAO Pei;LU Yonggang(Hebei Provincial Center for Disease Control and Prevention,Shijiazhuang 050051,China;不详)

机构地区：[1]河北省疾病预防控制中心,石家庄050051 [2]河北省人民医院

出　　处：《山东医药》2020年第29期39-42,共4页Shandong Medical Journal

基　　金：河北省医学科学研究重点课题计划(20170012)

摘　　要：目的探讨细颗粒物(PM 2.5)对Apo E基因敲除(Apo E-/-)小鼠动脉粥样硬化(AS)斑块及其内部巨噬细胞表型的影响。方法将32只8周龄雄性Apo E-/-小鼠(AS模型小鼠)随机分为两组,均给予高脂饲料喂养8周,同时对照组、PM 2.5组分别气管滴注生理盐水、PM 2.5生理盐水混悬液。8周后,采用电感耦合等离子体质谱法测定小鼠全血重金属含量,Movat染色法评估主动脉根部斑块面积,天狼星红染色检测斑块内胶原含量,免疫组化染色分别检测斑块内巨噬细胞(MAC-2阳性区域)和平滑肌细胞(β-actin阳性区域)数量,实时荧光定量PCR法检测降主动脉斑块中M1型[诱导型一氧化氮合酶(iNOS)、白细胞介素12(IL-12)]和M2型[精氨酸酶1(Arg-1)、CD206]巨噬细胞标志性因子基因。结果与对照组比较,PM 2.5组全血中重金属成分中铝、钒、铁含量升高,斑块面积增大,斑块中巨噬细胞数量增加、胶原含量降低,斑块内M1型巨噬细胞标志性因子iNOS、IL-12 mRNA表达增加而M2型巨噬细胞标志性因子CD206、Arg-1 mRNA表达下降(P均<0.05)。结论PM 2.5暴露促进了Apo E-/-小鼠AS的进展,其原因可能与动脉粥样斑块内巨噬细胞向M1表型倾斜有关。Objective To investigate the effect of fine particulate matter(PM 2.5)on atherosclerotic plaque and macrophage(Mφ)phenotype in Apo E knockout mice.Methods Thirty-two 8-week-old male Apo E-/-mice(atherosclerosis model mice)were randomly divided into two groups:the control group and PM 2.5 group.They were fed with high-fat diet for 8 weeks.At the same time,the mice in the control group and PM 2.5 group were intratracheal instilled with normal saline and PM 2.5 saline suspension,respectively.After 8 weeks,the content of heavy metals in whole blood of mice was measured by inductively coupled plasma mass spectrometry(ICP-MS).The plaque area of aortic root was evaluated by movat staining,and collagen content in plaque was detected by Sirius red staining.The expression of type M1(iNOS and IL-12)and type M2(Arg-1 and CD206)macrophage marker genes in descending aortic plaque was detected by real-time fluorescence quantitative PCR.Results Compared with the control group,the content of aluminum,vanadium and iron in whole blood of the PM 2.5 group increased,plaque area increased,macrophages increased,and the collagen content decreased.The expression of M1-type Mφgene markers(iNOS and IL-12)increased and the expression levels of M2 type Mφgene markers(Arg-1 and CD206)decreased in the plaque(all P<0.05).Conclusion PM 2.5 exposure promotes the progression of atherosclerosis in Apo E-/-mice,which may be related to the inclination of macrophages in atherosclerotic plaque to M1 phenotype.

关 键 词：动脉粥样硬化 主动脉斑块 细颗粒物 巨噬细胞表型 炎症 

分 类 号：R364[医药卫生—病理学]