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目的探讨急性冠状动脉综合征患者外周血单核细胞源性巨噬细胞表达过氧化体增殖物激活型受体γ、核因子κB、基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1的变化及其间的关系。方法选取急性冠状动脉综合征患者48例、稳定型心绞痛患者22例为研究对象,抽取外周动脉血20mL,分离单个核细胞,加巨噬细胞集落刺激因子培养得单核细胞源性巨噬细胞;用CD40配体刺激后,酶联免疫吸附法测定上清液中基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1浓度,逆转录聚合酶链反应检测过氧化体增殖物激活型受体γ、基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1mRNA表达,免疫组织化学法检测核因子κB亚单位P65表达。结果急性冠状动脉综合征组过氧化体增殖物激活型受体γmRNA表达低于稳定型心绞痛组(0.24±0.04比0.39±0.06,P<0.001),核因子κBP65表达高于稳定型心绞痛组(0.42±0.06比0.27±0.02,P<0.001),基质金属蛋白酶9在上清液中的浓度及其mRNA表达明显高于稳定型心绞痛组(231.11±51.47μg/L比126.02±13.26μg/L和0.674±0.11比0.24±0.05,P<0.001),组织型基质金属蛋白酶抑制剂1在上清液中的浓度及其mRNA表达强度高于稳定型心绞痛组(139.80±31.54μg/L比112.25±12.68μg/L和0.42±0.09比0.33±0.06,P<0.05)。过氧化体增殖物激活型受体γmRNA表达与核因子κBP65和基质金属蛋白酶9的表达强度呈负相关(P<0.001),与组织型基质金属蛋白酶抑制剂1的表达强度不相关(P>0.05);核因子κBP65与基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1的表达强度呈正相关(P<0.001)。结论急性冠状动脉综合征患者外周血单核细胞源性巨噬细胞过氧化体增殖物激活型受体γ表达下调,核因子κB活性增强,基质金属蛋白酶9和组织型基质金属蛋白酶抑制剂1表达上调;过氧化体增殖物激活型受体γ可能通过调节核因子κB活性而调节基质金属蛋白酶9基因转录;但组织型基质金属蛋白酶抑制剂1表达可能不受过氧化体增殖物激活型受体γ调节。
Objective To investigate the changes of expression of peroxisome proliferator - activated receptor γ, nuclear factor κB, matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinase - 1 in peripheral blood mononuclear cells of patients with acute coronary syndrome The relationship between. Methods Forty-eight patients with acute coronary syndrome and 22 patients with stable angina pectoris were enrolled in this study. Peripheral arterial blood was drawn from 20 mL of mononuclear cells and monocyte-derived macrophages were cultured with macrophage colony-stimulating factor. After stimulation with CD40 ligand, the concentrations of MMP-9 and TIMP-1 in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of peroxisome proliferator-activated receptor gamma Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression, immunohistochemical detection of nuclear factor kappa B subunit P65 expression. Results The mRNA expression of peroxisome proliferator-activated receptor γ in acute coronary syndrome group was significantly lower than that in stable angina group (0.24 ± 0.04 vs 0.39 ± 0.06, P <0.001), and the expression of nuclear factor κBp65 was higher than that in stable angina group ± 0.06 vs 0.27 ± 0.02, P <0.001). The concentration and mRNA expression of MMP-9 in the supernatant were significantly higher than those in the stable angina group (231.11 ± 51.47 μg / L vs 126.02 ± 13.26 μg / L and 0.674 ± 0.11 vs 0.24 ± 0.05, P <0.001). The concentration of tissue inhibitor of matrix metalloproteinase-1 and its mRNA expression in the supernatant were higher than those in the patients with stable angina (139.80 ± 31.54μg / L vs 112.25 ± 12.68μg / L and 0.42 ± 0.09 vs 0.33 ± 0.06, P <0.05). The expression of peroxisome proliferator - activated receptor gamma mRNA was negatively correlated with the expression of nuclear factor κBp65 and MMP - 9 (P <0.001), but not with the expression of tissue inhibitor of metalloproteinase - 1 (P> 0.05 ). Nuclear factor κBP65 was positively correlated with the expression of MMP-9 and MMP-9 (P <0.001). Conclusions The expression of peroxisome proliferator - activated receptor γ in peripheral blood mononuclear cells in patients with acute coronary syndrome is down - regulated, the activity of nuclear factor κB is enhanced, and the expression of matrix metalloproteinase - 9 and tissue inhibitor of metalloproteinase - 1 Upregulation. Peroxisome proliferator-activated receptor γ may regulate the transcription of matrix metalloproteinase 9 gene by regulating the activity of nuclear factor κB. However, the expression of tissue inhibitor of matrix metalloproteinase-1 may not be affected by the expression of peroxisome proliferator-activated receptor γ adjust.