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目的采用CD3抗体和IL-4/IL-4抗体复合物联合疗法,增加Tregs/Teffs比例,探讨其对于小鼠动脉粥样硬化的拮抗作用及免疫机制。方法 2014年5—11月采用高胆固醇饮食喂养载脂蛋白E缺陷性小鼠(apo E-/-)40只,随机分为对照组、γδTCR抗体组、IL-4复合物组及混合组各10只,分别使用空载体、CD3单克隆抗体、IL-4/IL-4抗体免疫复合物、CD3单克隆抗体-IL-4/IL-4抗体免疫复合物干预实验小鼠。检测各组小鼠动脉粥样硬化斑块形态、面积及稳定性、病变部位巨噬细胞及细胞间质含量、淋巴器官内Treg/Teff比例、脾脏单核细胞表型变化情况。计量资料采用方差分析,两两比较采用LSD-t检验,P<0.05为差异有统计学意义。结果四组脾脏及淋巴结CD4+T细胞/总细胞、CD25+Foxp3+细胞/CD4+细胞、CD25、CD103、类糖诱导TNF受体相关基因/蛋白(GITR)、细胞毒T细胞相关蛋白4(CTLA-4)、体重及血脂水平、Ly6C/单核细胞及CD115(CSF-1受体)水平比较差异均有统计学意义(均P<0.05)。混合组脾脏CD25+Foxp3+细胞/CD4+细胞、CD25、CD103、GITR、CTLA-4、甘油三酯、CD115水平均高于对照组,差异均有统计学意义(均P<0.05)。混合组淋巴结CD4+T细胞/总细胞、CD25+Foxp3+细胞/CD4+细胞、总胆固醇、低密度脂蛋白胆固醇、Ly6C/单核细胞水平均低于对照组,差异均有统计学意义(均P<0.05)。结论除了降低Teff介导的免疫反应外,增强Treg介导的免疫反应可更为有效的防治动脉粥样硬化,这可能是动脉粥样硬化治疗的新途径。
OBJECTIVE: To study the anti-atherosclerosis antagonism and immune mechanism of CD3 antibody and IL-4 / IL-4 antibody complex in combination with increasing Tregs / Teffs ratio. Methods Forty apolipoprotein E deficient mice (apo E - / -) were fed with high cholesterol diet from May to November in 2014 and randomly divided into control group, γδTCR antibody group, IL-4 complex group and mixed group 10 mice were randomly divided into experimental group and control group. The empty mice, CD3 monoclonal antibody, IL-4 / IL-4 antibody immune complex and CD3 monoclonal antibody-IL-4 / IL-4 antibody immune complex were used respectively to interfere the experimental mice. The morphology, area and stability of atherosclerotic plaque, the macrophages and interstitial contents in lesion, the Treg / Teff ratio in lymphoid organs and the phenotype of spleen mononuclear cells were detected. Measurement data were analyzed by ANOVA, pairwise comparisons using LSD-t test, P <0.05 for the difference was statistically significant. Results The expressions of CD4 + T cells / total cells, CD25 + Foxp3 + cells / CD4 + cells, CD25 + CD103, GITR / CTLA- 4), body weight and blood lipid levels, Ly6C / monocyte and CD115 (CSF-1 receptor) levels were significantly different (all P <0.05). The levels of CD25 + Foxp3 + cells / CD4 + cells, CD25, CD103, GITR, CTLA-4, triglyceride and CD115 in the mixed group were significantly higher than those in the control group (all P <0.05). The levels of CD4 + T cells / total cells, CD25 + Foxp3 + cells / CD4 + cells, total cholesterol, low density lipoprotein cholesterol and Ly6C / monocytes in the mixed group were significantly lower than those in the control group (all P < 0.05). Conclusion In addition to decreasing the Teff-mediated immune response, enhancing Treg-mediated immune responses may be more effective in preventing and treating atherosclerosis, which may be a new approach for the treatment of atherosclerosis.