主动脉夹层动物模型的建立及炎症细胞对主动脉夹层的影响

发布时间：2018-04-14 15:43

本文选题：主动脉夹层 + 炎症反应　；参考：《安徽中医药大学》2017年硕士论文

【摘要】：1目的考察主动脉夹层(Aortic dissection,AD)与炎症细胞浸润的因果关系,并且明确在AD发生过程中发挥重要作用的炎症细胞类型。2方法在考察AD疾病发生过程中炎症细胞浸润情况的研究中,通过调整饲料中β-氨基丙腈的含量建立两个AD疾病研究体系,分别为主动脉损害逐级严重的小鼠AD病程研究体系和24小时内血管撕裂甚至破裂的小鼠急性AD研究体系。在考察哪种炎症细胞参与AD发生的研究中,使用裸鼠(nu/nu)考察T淋巴细胞的作用,使用LysMi~(DTR)小鼠考察单核/巨噬细胞的作用。采用苏木素-伊红或地衣红染色进行血管组织结构评价;采用免疫组化考察炎症细胞浸润;采用免疫荧光方法对单核/巨噬细胞调控AD发生的分子机制开展研究。3结果基于主动脉损害逐级严重的小鼠AD病程研究体系发现炎症细胞在AD进程中的浸润逐渐增加,包括巨噬细胞、T淋巴细胞和中性粒细胞等,并且巨噬细胞在血管撕裂位置的浸润显著高于T淋巴细胞和中性粒细胞。基于24小时内血管撕裂甚至破裂的小鼠急性AD研究体系发现AD发生时炎症细胞的浸润急剧增加且以巨噬细胞为主。基于裸鼠的研究显示缺失T淋巴细胞对AD的发生没有显著影响;基于LysMi~(DTR)小鼠的研究显示,缺失单核/巨噬细胞能够显著抑制AD的发生,在LysMi~(DTR)小鼠上回输单核细胞则使AD的发生率增加。巨噬细胞与金属蛋白酶-9(MMP-9)共定位,并且敲除和回输单核细胞均伴随着对MMP-9表达水平的调控。4结论巨噬细胞在主动脉壁的浸润伴随着AD的形成,并且敲除单核/巨噬细胞能够保护主动脉的结构、抑制AD的发生,提示单核/巨噬细胞在AD发生的过程中扮演着重要角色。
[Abstract]:Objective to investigate the causal relationship between aortic dissection (AD) and inflammatory cell infiltration, and to identify the inflammatory cell type .2 which plays an important role in the development of AD.By adjusting the content of 尾 -aminopropionitrile in diet, two AD disease research systems were established, namely, the course of AD in mice with severe aortic damage, and the acute AD in mice with vascular tears or ruptures within 24 hours.In the study of which inflammatory cells were involved in AD, the effects of T lymphocytes in nude mice were examined by nu-nu-nu, and mononuclear / macrophage effects were examined in LysMi-DTR mice.Hematoxylin-eosin or lichen red staining was used to evaluate the vascular tissue structure, and immunohistochemistry was used to investigate the infiltration of inflammatory cells.The molecular mechanism of mononuclear / macrophage regulation of AD was studied by immunofluorescence method. Results based on the disease course study system of mice with severe aortic damage, the infiltration of inflammatory cells in AD process was gradually increased.The infiltration of macrophages at the location of vascular tear was significantly higher than that of T lymphocytes and neutrophils.Based on the acute AD research system in mice with vascular tears or ruptures within 24 hours, the infiltration of inflammatory cells was increased sharply and macrophages were the main type.Studies based on nude mice showed that deletion of T lymphocytes had no significant effect on the development of AD, and that deletion of mononuclear / macrophages could significantly inhibit the occurrence of AD in LysMi-DTR mice.The incidence of AD was increased in Lys Mignian DTR mice by transfusions of monocytes.Macrophages were co-located with metalloproteinase-9 (MMP-9), and both knockout and regurgitation monocytes were accompanied by regulation of MMP-9 expression level. Conclusion macrophage infiltration in aortic wall is associated with AD formation.Knockout mononuclear / macrophages can protect the aortic structure and inhibit AD, suggesting that monocytes / macrophages play an important role in the development of AD.
【学位授予单位】：安徽中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R543.1;R-332

【相似文献】