绝经后女性冠心病患者性激素水平与Toll样受体4及核因子-κB表达的相关性

Correlation of sex hormone with Toll-like receptor 4 and nuclear factor-kappa B in postmenopausal women with coronary heart disease

目的探讨绝经后女性冠心病患者Toll样受体4(Toll-like receptor 4,TLR4)及核因子-κB(nuclear factor-kappa B,NF-κB)表达与雌二醇(estradiol,E_2)、睾酮(testosterone,T)及E_2/T的关系。方法绝经后女性患者72例,其中24例急性冠状动脉综合征(acute coronary syndrome,ACS)患者为ACS组,24例稳定型心绞痛(stable angina pectoris,SAP)患者为SAP组,已排除冠心病的24例患者为对照组。应用实时荧光定量PCR法检测患者外周静脉血单核细胞TLR4和NF-κBp65mRNA表达水平,化学发光法测定血浆E_2及T水平,进行3组间比较,并分析变量间的相关性。结果ACS组TLR4、NF-κBp65mRNA表达水平(0.54±0.15、3.97±0.05)明显高于SAP组(0.27±0.09、2.66±0.16)及对照组(0.20±0.10、1.95±0.11)(P<0.05),且SAP组高于对照组(P<0.05);ACS组E_2、E_2/T[(47.15±1.79)pmol/L、63.11±14.29]低于SAP组[(54.19±4.69)pmol/L、138.5±14.29]及对照组[(75.01±4.96)pmol/L、239.91±11.26](P<0.05),SAP组低于对照组(P<0.05);TLR4与NF-κBp65 mRNA表达水平呈正相关(r=0.901,P=0.000),E_2与TLR4及NF-κBp65mRNA表达水平呈明显负相关(r=-0.654、P=0.000,r=-0.698、P=0.000),E_2/T与TLR4及NF-κBP65mRNA表达水平呈负相关(r=-0.426、P=0.000,r=-0.343、P=0.000)。结论绝经后女性冠心病患者TLR4及NF-κBp65mRNA表达升高、E_2和E_2/T水平下降,疾病的发生、发展与E_2/T失衡致抗炎、抗动脉粥样硬化作用减弱所致TLR4/NF-κB炎症通路过度激活有关。

Objective To explore the correlations of Toll-like receptor 4（TLR4）and nuclear factor-kappa B（NF-κB）with the serum levels of estradiol（E2）and testosterone（T）in the postmenopausal women with coronary heart disease（CHD）.Methods Seventy-two postmenopausal women were divided into acute coronary syndrome（ACS）group,stable angina pectoris（SAP）group and control group with no CHD,with 24 patients in each group.The expressions of TLR4 and NF-κBp65 mRNA in peripheral mononuclear cell were detected by real-time fluorescence quantitative PCR.The concentrations of plasma E2 and T were measured by chemiluminescence method.The above indexes were compared among three groups and their correlations between variables were analyzed.Results The expressions of TLR4 mRNA and NF-κBp65mRNA were significantly higher in ACS group（（0.54±0.15,3.97±0.05）than those in SAP group（0.27±0.09,2.66±0.16）and control group（0.20±0.10,1.95±0.11）（P〈0.05）,and were significantly higher in SAP group than those in control group（P〈0.05）.The levels of E2 and E2/T were significantly lower in ACS group（（47.15±1.79）pmol/L,63.11±14.29）than those in SAP group（（54.19±4.69）pmol/L,138.5±14.29）and control group（（75.01±4.96）pmol/L,239.91±11.26）（P〈0.05）,and were significantly lower in SAP group than those in control group（P〈0.05）.The expression of TLR4 was positively correlated with NF-κBp65 mRNA（r=0.901,P=0.000）,E2 was negatively correlated with TLR4（r=-0.654,P=0.000）and NF-κBp65 mRNA（r=-0.698,P=0.000）,and E2/T was also negatively correlated with TLR4（r=-0.426,P =0.000）and NF-κBp65 mRNA（r=-0.343,P=0.000）.Conclusion The expressions of TLR4 and NF-κB mRNA increase,and E2 and E2/T decrease in postmenopausal women with CHD.The development and progression of CHD are correlated with the excessive activation of TLR4/NF-κB inflammatory pathway caused by imbalanced E2/T ratio induced anti-inflammatory and anti-atherosclerosis weakening.