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

[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(P0.05)。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,P0.01)、Notch2(r=-0.468,P0.01)表达呈明显负相关,与Th1/Th2比值呈明显正相关(r=0.582,P0.01)。低、中、高剂量ox-LDL可明显阻滞Notch1、Notch2表达(P0.05)。[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。

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

[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.