二甲双胍对急性冠状动脉综合征患者血清组织因子的影响

摘要

目的 血清组织因子(tissue factor,TF)一定程度上反映了动脉硬化稳定性.文中研究二甲双胍对急性冠状动脉综合症(acute coronary syndrome,ACS)患者TF的影响.方法 抽取10名ACS患者空腹静脉血进行人单核细胞分离、培养,并分别予以终浓度为0、0.1、1和10μmol/L的二甲双胍进行干预,用酶联免疫吸附法检测培养细胞膜TF浓度.同时选取51名ACS患者根据服用药物分为常规治疗+二甲双胍组(n=29)和常规治疗组(n=22),4周后检测其外周循环血中TF的浓度,同时检测患者空腹血糖、血脂、胰岛素、C肽、C反应蛋白等相关指标.结果 二甲双胍组在0.1、1和10μmol/L浓度干预下测定的单核细胞膜TF值分别为(5.12±0.88)、(3.97±0.46)和(3.02±0.88)pg/ml,差异有统计学意义(P＜0.05).在51名ACS患者外周循环血中,常规治疗+二甲双胍组与常规治疗组的TF分别为(57.63±23.75)和(98.25±20.50)pg/ml(P＜0.05),同时低密度脂蛋白[(1.99±0.32)vs(2.99±0.56)mmol/L]、血糖[(5.38±1.88)vs(6.47±0.78)mmol/L]、C肽[(6.86±4.24)vs(10.83±3.08)ng/ml]及CRP[(8.32±1.24)vs(16.66±2.34)ng/ml]等相关指标均有统计学意义(P＜0.05).结论 二甲双胍可降低ACS患者外周血单核细胞合成TF的表达,并呈现浓度依赖性,在ACS患者中二甲双胍可改善血脂异常,提高胰岛素敏感性,降低ACS患者循环血中TF表达.%Objective The serum tissue factor (TF) reflects the stability of atherosclerosis. This study investigates the effects of metformin on TF in patients with acute coronary syndrome ( ACS). Methods In the first part of the scudy, 10 patients with ACS were subjected to peripheral blood sampling. The peripheral human monocytes were cultured with metformin (0, 0.1 , 1 or 10 μmol/L) , 24 hours , the expression of TF were investigated. In the second part of the study, 51 patients with ACS were enrolled. Patients were randomized to conventional therapy + metformin therapy group ( n = 29) or conventional therapy group (n = 22). The levels of TF in serum, blood lipids, blood glucose and insulin, as well as C peptide and C-reactive protein expression, were studied after therapy four weeks. Results In vitro, a dose-dependent effect of TF expression on monocytes membrane in cultured peripheral blood monocytes was found , the TF levels in 0. 1 , 1 and 10 μmol/L metformin groups were 5. 12 ± 0. 88 , 3. 97 ± 0. 46 and 3. 02 ± 0. 88 pg/ml, respectively. In vivo, treatment of conventional + metformin reduced the expression of TF, compared with that of conventional only (57. 63 ± 23. 75pg/ml vs 98. 25 ± 20. 50pg/ml, P ＜ 0. 05 ) , there were significant differences in blood lipids , blood glucose , C peptide, and C-reactive protein expression between the metformin group and the placebo group . Conclusion For patients with ACS, metformin can inhibit TF expression on monocytes in a concentraliondependent pattern, it also improves blood lipid abnormalities and insulin sensitivity.