ho-1调节适应性免疫反应对apoe--小鼠动脉粥样硬化作用机制分析word论文.docxVIP

HO-1 调节适应性免疫反应对 ApoE-/-小鼠动脉粥样硬化作用机制研究研究生：吴帮卫导 师：曾秋棠 教授中文摘要目的：探讨效应性/调节性 T 淋巴细胞反应平衡是否参与血红素氧合酶-1（heme oxygenase, HO-1）对 ApoE-/-小鼠动脉粥样硬化保护作用。方法和结果：8 周龄雄性 ApoE-/-小鼠随机分为三组，给予 8 周西方饮食的同时，分 别经腹腔注射 Hemin（诱导 HO-1，HO-1 组），Zn-protoporphyrin IX（抑制 HO-1，Zn 组），和生理盐水（对照组），并维持 8 周。与对照组相比，HO-1 组动脉内 HO-1 表 达以及 HO-1 活性明显增加，伴随血浆脂质氢过氧化物（plasma lipid hydroperoxide ， LPO）浓度降低。同时，HO-1 组主动脉根处斑块显著减轻，且斑块更稳定，表现为 平滑肌细胞、胶原纤维帽增厚，而巨噬细胞和 CD4+细胞减少。进一步研究发现，小 鼠脾脏 Th1, Th2, 和Th17 数目在 HO-1 组显著降低，而调节性 T 细胞 （CD4+CD25+Foxp3+）明显增高，同时血清中细胞因子 IFN-r， IL-4， IL-17，IL-6 表达下降，而 IL-10， TGF-β上调，主动脉内 Foxp3 表达增加。Zn 组检测结果显示 斑块明显加重，更趋于易损状态，且效应性/调节性 T 细胞（主要为 Th17/Treg）比例 失平衡。结论：HO-1 对 ApoE-/-小鼠动脉粥样硬化具有保护作用，这可能和抑制效应性 T 而促 进调节性 T 细胞反应相关。关键词：动脉粥样硬化；HO-1;效应性 T 细胞；调节性 T 细胞AbstractObjective：HO-1 shows a strong ability of antioxidant stress and anti-inflammatory response, identified as a promising therapeutic target for vascular inflammatory disease including atherosclerosis. The aim of this study was to investigate if HO-1 amelioratesatherosclerosis by modulating the balance of effector and regulatory T cells in ApoE-/- mice.Methods and Results：Intraperitoneal injections of hemin to induce HO-1 (HO-1 group),or Zn-protoporphyrin IX to inhibit HO-1 (Zn group), and saline as control (Control group) were performed on 8 week old male ApoE-/- mice fed with western diet for 8 weeks. Compared with Control group, the arterial expression and activity of HO-1, and the plasma lipid hydroperoxide (LPO) levels were significantly increased in HO-1 group, which showed obviously less mean atherosclerotic lesions in the aortic root, characteristic with increased smooth muscle cells, higher collagen concentration, however, decreased CD4+T cells and macrophages featuring a stable plague. Furthermore, the number of Treg (CD4+CD25+Foxp3+) was markedly increased in the spleens of mice in HO-1 group, whereas the Th1, Th2, and Th17 cells were reduced, accompanied with related cytokines and gene expression altered accordingly in lesions and plasm