丹参酮ⅡA磺酸钠联合阿托伐他汀对冠心病患者外周血单个核细胞TLR4、MyD88、NF-κB表达的影响

摘要

目的：观察冠心病患者外周血单个核细胞 TLR4、MyD88、NF-κB 的表达，分析丹参酮ⅡA 磺酸钠联合阿托伐他汀对其表达的影响，以 TLR4炎症信号通路为靶点探讨丹参酮ⅡA 磺酸钠治疗冠心病的可能机制。方法选取诊治的冠心病患者160例，同期进行健康体检的正常人100例作为对照。采用 Real time-PCR 和 Western blot 测定外周血单个核细胞 TLR4、MyD88、NF-κB mRNA 和蛋白表达，采用酶联免疫吸附实验（ELISA）测定血清高敏 C-反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）水平。160例冠心病患者随机分为观察 A 组和观察 B 组，每组80例。观察 A 组在常规治疗基础上给予阿托伐他汀治疗，观察 B 组在观察 A 组基础上加用丹参酮ⅡA 磺酸钠注射液，疗程均为30 d，比较2组 TLR4、MyD88、NF-κB mRNA 和蛋白表达、hs-CRP、TNF-α水平。结果与对照组比较，冠心病患者组 TLR4、MyD88、NF-κB mRNA 和蛋白表达、hs-CRP、TNF-α水平显著升高（ P ﹤0.05）。TLR4、MyD88、NF-κB 蛋白表达与 hs-CRP、TNF-α呈正相关（ r ＝0.761和0.802，0.699和0.774，0.835和0.749，P 均﹤0.05）。与治疗前比较，治疗后观察 A 组和观察 B 组 TLR4、MyD88、NF-κB mRNA 和蛋白表达、hs-CRP、TNF-α水平均显著降低（ P ﹤0.05）；但观察 B 组降低程度更明显（ P ﹤0.05）。结论丹参酮ⅡA 磺酸钠联合阿托伐他汀通过抑制外周血单个核细胞 TLR4炎症信号通路的激活发挥抗炎作用，可能是丹参酮ⅡA 磺酸钠发挥治疗作用的机制之一。%Objective To observe the expressions of TLR4,MyD88 and NF-κB in peripheral blood mononuclear cells of patients with coronary heart diseases(CHD),and to investigate the effects of sodium tanshinone ⅡA sulfonate combined with atorvastatin on the expression levels of TLR4,MyD88 and NF-κB in order to explore the action mechanism of sodium tanshinone Ⅱ A sulfonate in treatment of CHD. Methods One hundred and sixty patients with CHD were enrolled as observation group,and 100 healthy subjects were served as control group. The expression levels of TLR4,MyD88 and NF-κB in peripheral blood mononuclear cells were detected by Real time-PCR and Western Blot,moreover,the serum levels of hs-CRP and TNF-α were detected by ELISA. The 160 patients in observation group were redivided into observation group A and observation group B,with 80 patients in each group. The patients in observation group A,on the basis of routine therapy, were treated with atorvastatin,however,the patients in observation group B,on the basis of observation group A,were given sodium tanshinone ⅡA sulfonate injection,with a treatment course of 30 days for both groups,finally the expression levels of TLR4,MyD88,NF-κB mRNA and protein,hs-CRP and TNF-αwere detected and compared between the two groups. Results As compared with those in control group,the expression levels TLR4,MyD88,NF-κB mRNA and protein,hs-CRP and TNF-αwere significantly increased in observation groups( P ﹤ 0. 05). Furthermore the expressions of TLR4,MyD88,NF-κB protein were positively correlated to those of hs-CRP and TNF-α( P ﹤ 0. 05). As compared with those before treatment,the expression levels TLR4,MyD88,NF-κB mRNA and protein,hs-CRP,TNF-αwere significantly decreased after treatment in both observation groups(P ﹤ 0. 05),but the decrease degree in observation group B was more significant than that in observation group A( P ﹤ 0. 05). Conclusion Sodium tanshinone ⅡA sulfonate combined with atorvastatin can significantly restrain the activation of TLR4 signal transduction pathway,which may be one of action mechanisms of sodium tanshinone Ⅱ A sulfonate in treatment of CHD.