IL-23/IL-17炎症轴在病毒性心肌炎小鼠中的表达及意义

摘要

目的：观察白介素（IL）-23/IL-17炎症轴在病毒性心肌炎（VMC）小鼠中表达的动态变化，并探讨其意义。方法将60只BALB/c小鼠随机分为VMC组（n=50）和对照组（n=10）。VMC组腹腔注射0.1 ml含柯萨奇B3病毒（CVB3）的Eagle’s液建立VMC模型，分别于接种后第7、14、28天随机各取10只处死；对照组腹腔注射0.1 ml不含CVB3的Eagle’s液，于第28天处死。通过苏木精-伊红（HE）染色检查心肌病理改变，并计算心肌病理积分；采用荧光实时定量PCR、Western blotting检测心肌IL-23及IL-17的mRNA、蛋白表达水平；采用酶联免疫吸附法测定血清IL-23、IL-17浓度；并对VMC组血清IL-23、IL-17浓度与心肌病变积分之间的相关性进行分析。结果 VMC组接种病毒后第7、14、28天心肌病理积分， IL-23和IL-17 mRNA及蛋白表达水平，以及血清IL-23、IL-17水平均高于对照组，差异有统计学意义（P均<0.01）；其中接种病毒后第7天，VCM组的各项指标均处于最高水平，随后逐渐下降，在各时间点各项指标的差异均有统计学意义（P均<0.05）；VMC组的血清IL-23、IL-17水平与心肌病理积分呈正相关（r=0.73、0.76，P均<0.05）。结论 IL-23/IL-17炎症轴在VMC的发病过程中可能起重要作用，并与VMC病情严重程度密切相关。%Objective To observe the dynamic changes of interleukin-23 (IL-23)/interleukin-17 (IL-17) inflammatory axis expression in the myocardium of mice with viral myocarditis (VM) and further to explore its significance. Methods A total of 60 BALB/c mice were randomly divided into VMC group (n=50) and control group (n=10). Mice in VMC group were intraperito-neally inoculated with 0.1ml Eagle's solution containing coxsackievirus B3 (CVB3) to establish VM model and 10 mice were sacri-ficed each time at days 7, 14 and 28 after inoculation. Mice in control group were treated with 0.1ml Eagle's solution without CVB3 and all the 30 mice were killed on day 28 after inoculation. Myocardial histopathologic changes were detected with hema-toxylin and eosin (HE) staining and myocardial histopathological scores were calculated. The expression levels of myocardial IL-23/IL-17 mRNA and protein were determined by real-time quantitative PCR and immunohistochemistry, respectively. Serum IL-23 and IL-17 concentrations were examined using ELISA. Also, the relationship between serum IL-23 and IL-17 concentra-tions and myocardial histopathological scores was analyzed in VMC group. Results At days 7, 14 and 28 after inoculation, the myocardial histopathological scores, mRNA and protein expressions of myocardial IL-23/IL-17 and serum IL-23 and IL-17 con-centrations were significantly higher in VMC group than those in control group (P<0.01). Each of the above indicators reached its highest level on 7th day after inoculation (P<0.01) and then gradually decreased. There were significant differences among dif-ferent time points (P<0.05). Serum IL-23 and IL-17 concentrations showed significantly positive correlation with the myocardi-al histopathologic scores in VMC group, respectively (r=0.73 and 0.76, P<0.05). Conclusions IL-23/IL-17 inflammatory axis may play an important role in the process of VMC and is closely associated with the severity of VMC.