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目的在人类冠心病的研究中,调节性T细胞的变化水平存在争议。实验证明FOXP3基因的去甲基化状态保证其基因能够稳定表达,是调节性T细胞发挥抑制性功能的基础。研究还发现了一项新的调节性T细胞的检测方法,即基于调节性T细胞FOXP3基因特殊区域(TSDR)的去甲基化水平来反应调节性T细胞的水平。所以本研究旨在应用这种新的方法来评估冠心病患者调节性T细胞水平。方法和结果本研究纳入20位ST段抬高的急性心肌梗死患者,16位非ST段抬高的急性冠脉综合征患者以及20位冠脉造影正常者。分离外周血单个核细胞,分别用流式细胞分析仪和基于PCR的FOXP3基因甲基化分析来测量调节性T细胞水平。实验发现,冠心病患者用基于PCR的FOXP3基因甲基化分析所得到的调节性T细胞水平均是降低的(正常对照4.22%±1.92%,非ST段抬高的急性冠脉综合征3.29%±1.45%;ST段抬高的急性心肌梗死2.86%±1.26%),而流式细胞仪所得到的调节性T细胞水平在冠心病患者中的改变不一致。FOXP3-TSDR的去甲基化水平与冠心病的严重程度呈反比(r=-0.308,P<0.05)。在去除传统危险因素的影响后,这种相关性依然显著存在(β=-0.336,P<0.05)。结论本研究显示冠心病患者的去甲基化FOXP3所代表的调节性T细胞水平显著降低,调节性T细胞的减少和动脉粥样硬化的严重程度呈负相关关系。
Objective In the study of human coronary heart disease, the level of regulatory T cells is controversial. Experiments show that FOXP3 gene demethylation status to ensure that its gene can be stably expressed, regulatory T cells play a suppressive function. The study also found a new test for regulatory T cells that responds to regulatory T-cell responses based on the demethylation level of the special region of the regulatory T-cell FOXP3 gene (TSDR). Therefore, this study aims to apply this new method to assess the level of regulatory T cells in patients with coronary heart disease. Methods and Results In this study, 20 patients with acute ST-segment elevation myocardial infarction, 16 patients with non-ST elevation acute coronary syndrome, and 20 patients with normal coronary angiography were enrolled. Peripheral blood mononuclear cells were isolated and regulatory T-cell levels were measured by flow cytometry and PCR-based FOXP3 gene methylation analysis, respectively. The experiment found that patients with coronary heart disease PCR-based FOXP3 gene methylation analysis of the resulting regulatory T-cell levels were reduced (normal control 4.22% ± 1.92%, non-ST-segment elevation acute coronary syndrome 3.29% ± 1.45%; ST segment elevation acute myocardial infarction 2.86% ± 1.26%), while the level of regulatory T cells obtained by flow cytometry was inconsistent in patients with coronary heart disease. The demethylation level of FOXP3-TSDR was inversely proportional to the severity of coronary heart disease (r = -0.308, P <0.05). After removing the influence of traditional risk factors, the correlation still existed (β = -0.336, P <0.05). CONCLUSIONS: This study shows that patients with coronary heart disease have a significantly reduced level of regulatory T cells, as demonstrated by demethylation of FOXP3, and a negative correlation between reduced T regulatory cells and the severity of atherosclerosis.