转录因子BACH2在冠心病患者外周血单个核细胞中的表达及意义

Expression of transcription factor BACH2 and its significance on PBMC in patients with coronary artery disease

目的:研究转录因子BACH2在冠心病(CAD)患者外周血单个核细胞中的表达水平,并探讨其在冠心病发病中的意义及作用机制。方法:采用密度梯度离心法分离急性冠脉综合征(ACS)、稳定型心绞痛(SA)和正常对照组(NS)三组受试者外周血单个核细胞(PBMC);采用RT-PCR和Western blot法检测不同组别PBMC中BACH2及TLR4的表达量;采用ELISA法检测不同组别血清ox-LDL及TH1,TH2,TH17和Treg细胞各自标志性细胞因子(IFN-γ,IL-4,IL-17和TGF-β1)的水平。组间差异的比较使用方差齐性分析,各变量之间的相关性使用直线回归分析。结果:ACS组病人PBMC中的BACH2表达显著下调,TLR4表达显著上调。ACS组血清ox-LDL及IFN-γ、IL-4、IL-17水平较SA组和NC组显著升高,而TGF-β1显著降低。CAD患者PBMC中的BACH2表达量与TLR4表达水平显著负相关;BACH2表达量与IFN-γ、IL-4和IL-17水平负相关,与TGF-β1水平显著正相关。结论:冠心病患者循环中的BACH2表达降低;CAD病人循环中高浓度的ox-LDL可能通过激活TLR4抑制BACH2的表达,进而造成CD4^+T细胞亚群分化和发育失调以及炎症因子分泌紊乱,从而导致冠心病的发生和发展。

Objective：To investigate the expression of transcription factor BACH2 on PBMC in patients with coronary artery disease（CAD） and discuss its significance and role. Methods： The circulating levels of BACH2 and TLR4 in PBMC were evaluated by RT-PCR and Western blot separately. Serum levels of signature cytokines of T-helper cells, cytokines and ox-LDL were evaluated by ELISA. The data among groups were analyzed by one-way ANOVA. Correlation between variables were subjected to linear regression analysis. Results： The expression level of BACH2 down-regulated and TLR4 up-regulated significantly in PBMCs of ACS patients had significantly higher concentrations of serum ox-LDL, Cytokines of TH1 ceils, TH2 cells and TH17 cells and low level of cytokine of Treg cells. Negative correlation exists significantly between BACH2 and TLR4 in patients with CAD and between BACH2 and 1FN-γ, IL-4 and IL-17,and between BACH2 and ox-LDL in serum. However, positive correlation exists significantly between BACH2 and TGF- 131. Conclusion： Increased serum concentrations of ox-LDL probably down-regulated the expression of BACH2 in ACS patients by activating TLR4 on PBMC, resulting in promoting production of pro-inflammatory cytokines and suppressing production of anti- inflammatory cytokine and then might cause ACS.