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目的探讨罗格列酮干预对冠心病患者外周血单核细胞源性巨噬细胞(MDMs)表达核因子-κB(NF-κB)、基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制物1(TIMP-1)中的影响。方法提取急性冠脉综合征(ACS)患者和稳定型心绞痛(SA)患者外周血单个核细胞,加巨噬细胞集落刺激因子培养得MDMs;分亚组用不同浓度罗格列酮干预;免疫组化法测定各亚组MDMs表达NF-κB亚单位P65(NF-κB P65),RT-PCR测定MMP-9和TIMP-1 mRNA的表达。分析比较ACS组与SA组间及不同浓度罗格列酮亚组间在表达NF-κB P65、MMP-9和TIMP-1 mRNA上的差异。结果罗格列酮干预使ACS组及SA组MDMs表达MMP-9 mRNA下调;ACS组MDMs表达NF-κB P65下调;对两组中MDMs表达TIMP-1 mRNA无影响。ACS组MDMs表达MMP-9 mRNA及NF-κB P65水平显著高于SA组。结论 ACS患者外周血MDMs表达MMP-9 mRNA及NF-κB P65水平显著高于SA组。罗格列酮干预可抑制ACS组外周血MDMs的NF-κB活性,在转录水平上抑制ACS患者和SA患者的外周血MDMs表达MMP-9;但不影响TIMP-1 mRNA表达。
Objective To investigate the effects of rosiglitazone on the expression of nuclear factor-κB (NF-κB), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase inhibitor (MMP) in peripheral blood mononuclear cells from patients with coronary heart disease 1 (TIMP-1) in the impact. Methods Peripheral blood mononuclear cells from patients with acute coronary syndrome (ACS) and patients with stable angina pectoris (SA) were collected and cultured with macrophage colony stimulating factor (MDMs). The subgroups were treated with rosiglitazone at different concentrations. The expression of NF-κB subunit P65 (NF-κB P65) in each subgroup of MDMs was measured by immunohistochemistry. The expressions of MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The difference between the expression of NF-κB P65, MMP-9 and TIMP-1 mRNA in ACS group and SA group and between different concentrations of rosiglitazone subgroup was analyzed. Results Rosiglitazone down-regulated the expression of MMP-9 mRNA in MDMs in ACS group and SA group. The expression of NF-κB P65 in MDMs in ACS group was down-regulated. The expression of TIMP-1 mRNA in MDMs was not affected in both groups. The expression of MMP-9 mRNA and NF-κB P65 in MDMs in ACS group was significantly higher than that in SA group. Conclusion The expression of MMP-9 mRNA and NF-κB P65 in peripheral blood of ACS patients was significantly higher than that of SA patients. Rosiglitazone could inhibit NF-|ÊB activity in MDMs in peripheral blood of ACS patients and inhibit the expression of MMP-9 in peripheral blood of ACS patients and SA patients at the transcriptional level, but did not affect the expression of TIMP-1 mRNA.