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目的:研究白细胞介素17A(IL-17A)对柯萨奇B3(CVB3)病毒性心肌炎(VMC)小鼠病毒复制的影响及其可能的机制。方法:雄性Balb/c小鼠野生型(WT)和IL-17A基因敲除型(IL-17A-/-)分别感染CVB3建立VMC模型(WT-VMC组和IL-17A-/--VMC组),同时雄性Balb/c WT小鼠腹腔内注射PBS建立对照组(WT-PBS组)。14d后分别留取小鼠心脏及脾脏,计算心体比(HW/BW)并行HE染色观察心肌病理,心肌空斑法测定CVB3病毒滴度,RT-PCR法测定心肌中CVB3RNA、γ干扰素(IFN-γ)mRNA的表达,流式细胞分析法检测脾Th1细胞亚群的比例(CD4+Th1),Western blot法测定心肌中转录因子T-bet蛋白的表达。结果:与WT-PBS组相比,WT-VMC组小鼠心肌炎症明显,HW/BW及心肌病理积分显著升高,CVB3病毒滴度、CVB3RNA及IFN-γmRNA的表达、脾CD4+Th1细胞比例、心肌T-bet蛋白表达均明显升高(均P<0.05)。与WT-VMC组相比,IL-17A-/--VMC组小鼠心肌的炎症程度明显减轻,HW/BW及病理积分减小,CVB3病毒滴度与CVB3RNA的表达明显下降(均P<0.05),而IFN-γmRNA的表达、脾CD4+Th1细胞比例、心肌T-bet蛋白的表达均较WTVMC组明显升高(均P<0.05)。结论:IL-17A抑制VMC小鼠的抗病毒免疫功能,促进CVB3病毒复制,其机制可能与抑制T-bet表达有关。
Objective: To investigate the effect of interleukin 17A (IL-17A) on virus replication in Coxsackievirus B3 (CVB3) viral myocarditis (VMC) mice and its possible mechanism. Methods: The VMC model was established in both CVB3 and WT-VMC and IL-17A - / - VMC groups in male Balb / c mice infected with WT and IL-17A knockout mice respectively ), While male Balb / c WT mice were intraperitoneally injected with PBS to establish a control group (WT-PBS group). After 14 days, the heart and spleen of the mice were collected, and the cardiomyopathies were observed by HE staining and the CVB3 virus titers were measured by plaque assay. The expressions of CVB3, IFN-γ IFN-γ) mRNA was detected by flow cytometry. The percentage of Th1 cell subsets in spleen was measured by flow cytometry (CD4 + Th1), and the expression of T-bet in myocardium was detected by Western blot. Results: Compared with WT-PBS group, the myocardium inflammation of WT-VMC group was significantly increased, the scores of HW / BW and cardiomyopathy were significantly increased, the CVB3 virus titer, the expression of CVB3 and IFN-γmRNA, the proportion of splenic CD4 + Th1 cells , Myocardial T-bet protein expression were significantly increased (all P <0.05). Compared with the WT-VMC group, the inflammation in the myocardium of IL-17A - / - VMC group was significantly reduced, the HW / BW and pathological score were decreased, the CVB3 virus titer and the expression of CVB3RNA were significantly decreased (all P <0.05 ), While the expression of IFN-γmRNA, the proportion of splenic CD4 + Th1 cells and the expression of T-bet protein in myocardium were significantly higher than those in WTVMC group (all P <0.05). Conclusion: IL-17A inhibits the anti-viral immune function of VMC mice and promotes the replication of CVB3 virus, which may be related to the inhibition of T-bet expression.