Toll样受体3信号通路在人类病毒性心肌炎心肌细胞凋亡及炎症反应中的作用

Toll-like receptor 3 signaling pathway plays an important role in cardiomyocyte apoptosis and inflammatory response in human viral myocarditis

目的:研究Toll样受体3(TLR3)信号转导通路与人类病毒性心肌炎(VMC)炎症反应及细胞凋亡的关系。方法:采用免疫组化SP法分别检测TLR3、干扰素βTIR结构域衔接蛋白(TRIF)、核因子κB(NF-κB)及半胱氨酸天冬氨酸蛋白酶3(caspase-3)在心肌组织中的变化,原位末端标记法(TUNEL)检测心肌细胞凋亡情况,比较VMC组及正常对照组组间的差异。结果:与对照组比较,VMC组心肌组织中TLR3、TRIF、NF-κB及caspase-3蛋白表达及细胞凋亡水平明显增高,差异有统计学意义(P<0.05),并且TLR3和TRIF、TLR3和NF-κB、TRIF和NF-κB、NF-κB和caspase-3之间的表达均呈正相关,细胞凋亡指数的变化趋势与caspase-3一致。结论:通过TLR3信号通路介导的炎症反应和细胞凋亡在VMC发生、发展过程中起着重要作用,抑制其活化有可能成为治疗VMC的一个潜在的、有价值的靶位。

AIM ： To investigate the role of the signaling pathway mediated by Toll-like receptor 3 （TLR3） in cardiomyocyte apoptosis and inflammatory response in human viral myocarditis （VMC）. METHODS： The expression of TLR3, TIR domain-containing adaptor inducing IFN-I3（TRIF） , NF-KB and casepase-3 in myocardial tissues was examined by the method of immunohistochemistry with SP staining, and the apoptosis of cardiomyocytes was detected by terminal de- oxynucleotidyl transferase （TdT）-mediated dUTP nick end labeling （TUNEL）. The differences between VMC and control groups were analyzed. RESULTS ： Compared with control group, the expression of TLR3, TRIF, NF-KB and casepase-3, and the apoptotic index in VMC group increased remarkably （P 〈 0.05 ）. The positive correlations between TLR3 and TRIF, between TLR3 and NF-KB, between TRIF and NF-KB, and between NF-KB and caspase-3 were observed. The change of the apoptotic index was in accordance with that of caspase-3. CONCLUSION ： Inflammatory response and apop- tosis mediated by TLR3 play an important role in the genesis and development of viral myocarditis.