氧化型低密度脂蛋白与急性冠状动脉综合征患者CD4+T细胞Notch1、Notch2表达的相关性研究

Association among oxidized low density lipoprotein and the expression of Notch1,Notch2 in CD4+ T cells in patients with acute coronary syndrome

关键词:  急性冠状动脉综合征  氧化型低密度脂蛋白  Th1/Th2细胞  Notch1  Notch2

Key words:  acute coronary syndrome  oxidized low density lipoprotein  Th1/Th2 cell  Notch1  Notch2

摘要:

[目的]探讨氧化型低密度脂蛋白（ox-LDL）与急性冠状动脉综合征（ACS）患者CD4⁺T细胞Notch1、Notch2表达的相关性研究。[方法]纳入健康对照人群30例，稳定型心绞痛（SA）患者32例，ACS患者56例[不稳定型心绞痛（UA）患者30例，急性心肌梗死（AMI）26例]，收集外周血标本，酶联免疫吸附测定（ELISA）试剂盒检测ox-LDL表达，流式细胞仪检测CD4⁺T细胞Notch1、Notch2分子的表达变化及Th1/Th2比值改变。采用流式细胞术分选CD4⁺T细胞，利用低、中、高剂量ox-LDL（0、40、80、160 mg/L）刺激细胞72 h，利用流式细胞仪检测CD4⁺T细胞Notch1、Notch2分子的表达变化。[结果]UA组、AMI组CD4⁺T细胞Notch1、Notch2表达明显降低，而Th1/Th2比值及ox-LDL水平明显升高（P<0.05）。经Pearson相关性分析发现，ACS患者（UA组、AMI组）外周血ox-LDL与Notch1（r=-0.653，P<0.01）、Notch2（r=-0.468，P<0.01）表达呈明显负相关，与Th1/Th2比值呈明显正相关（r=0.582，P<0.01）。低、中、高剂量ox-LDL可明显阻滞Notch1、Notch2表达（P<0.05）。[结论]ox-LDL能明显抑制人外周血CD4⁺T细胞Notch1、Notch2分子表达，可能与ox-LDL抑制Th2分化而促进Th1异常分化有关。

Abstract:

[Objective] To study the association between oxidized low density lipoprotein (ox-LDL) and the expression of Notch1,Notch2 in CD4⁺ T cells in patients with acute coronary syndrome.[Methods] The 26 patients with acute myocardial infarction (AMI),30 patients with unstable angina (UA),32 patients with stable angina (SA) and 30 healthy subjects (NC) were recruited. The plasma level of ox-LDL was measured by ELISA,and the ratio of Th1/Th2 and the expression of Notch1,Notch2 in CD4⁺ T cells in peripheral blood were detected by flow cytometry. Then CD4⁺ T cells were sorted by flow cytometry,T cells were cocultured with varying concentrations of ox-LDL (0,40,80,160 mg/L),the expression of Notch1 and Notch2 in CD4⁺ T cells were detected by flow cytometry in each group after 72 h.[Results] The expression levels of Notch1,Notch2 in CD4⁺ T cells were greatly decreased,the ratio of Th1/Th2 and the level of ox-LDL were significantly increased in AMI group and UA group compared with NC group (P<0.05). Pearson correlation analyses indicated that ox-LDL was significantly and negatively associated with the expression of Notch1 (r=-0.653,P<0.01) and Notch2 (r=-0.468,P<0.01) in patients with acute coronary syndrome,and ox-LDL was significantly and positively associated with the ratio of Th1/Th2 (r=0.582,P<0.01).[Conclusions] ox-LDL can obviously inhibit the expression of Notch1 and Notch2 in human peripheral blood CD4⁺ T cells,which may be the reason that ox-LDL inhibit the differentiation of Th2 and promote the differentiation of Th1,and participate in the occurrence and development of atherosclerosis.