白细胞介素-17A调节转化生长因子β1对病毒性心肌炎小鼠心肌纤维化的影响

目的 在小鼠病毒性心肌炎（viral myocarditis,VMC）心肌纤维化的发展过程中,观察白细胞介素-17A（interleukin-17A,IL-17A）是否通过调节转化生长因子-β1（transforming growth factor-β1,TGF-β1）参与心肌纤维化.方法 IL-17A基因敲除（IL-17A-deficient,IL-17A-/-）Balb/c小鼠和野生型（wild-type,WT） Balb/c小鼠分别按电脑随机数字表法分为4组,腹腔注射TCID50为10-5的柯萨奇病毒B3 （coxsackie virus B3,CVB3） 0.1 mL培养液建立小鼠VMC模型,于注射病毒后第0、14、28和42天处死小鼠,然后无菌取心脏组织,苏木素-伊红和Masson染色观察心肌组织形态学,并分别计算心肌病理积分和胶原容积积分（CVF）.实时荧光定量聚合酶链反应检测心肌组织TGF-β1mRNA的表达;酶联免疫吸附测定法检测心肌组织TGF-β1蛋白的表达水平.结果 WT小鼠的心肌纤维化随着VMC的病程发展不断加重,TGF-β1于14 d表达显著升高,28 d和42 d后逐渐下降,但仍高于正常水平,差异有统计学意义（P＜0.05）.与同时点WT小鼠相比,IL-17A-/-小鼠心肌组织的心肌纤维化程度明显减轻,TGF-β1mRNA和蛋白的表达水平明显降低,差异有统计学意义（P＜0.05）.结论 IL-17A参与VMC的心肌纤维化过程,并可能通过调节TGF-β1的表达而参与这一过程.

Influence of interleukin-17A on the pathogenesis of myocardial fibrosis by inducing transforming growth factor β1 in mice with viral myocarditis

Objectives To investigate whether interleukin-17A （IL-17A） contributes to the pathogenesis of myocardial fibrosis by inducing transforming growth factor 31 （TGF-I31） in mice with viral myocarditis （VMC）. Methods IL-17A- deficient （IL-17A-/-） and wild-type （WT） mice on the Balb/c background were intraperitoneally （i.p） injected with 0.1 mL coxsackievirus B3 （CVB3）（ 10-5 TCID50）for establishing VMC models. Each group was randomly divided into 4 subgroups by random number method. Surviving mice were separately sacrificed and heart tissues were collected on day 0, 14, 28 and 42 after CVB3 infection. Hematoxylin-eosin and Masson staining were performed for histological analysis. Furthermore, myocardial histopathologic scores and collagen volume fraction （CVF） were calculated. Cardiac protein and mRNA levels of TGF-β1 were measured by real-time polymerase chain reaction （PCR） and enzyme-linked immunosorbent assay （ELISA） respectively. Results Myocardial fibrosis elevated during the development of VMC in WT mice; expression of TGF-β1 increased obviously on day 14 after CVB3 infection, and then reduced gradually on day 28 and 42, but still higher than normal （P〈0.05）. Compared with WT mice, IL-17A-/- mice developed much less severe myocardial fibrosis and levels of TGF-β1 mRNA and protein were significantly lower （P〈0.05）. Conclusions IL-17A may be involved in the pathogenesis of myocardial fibrosis by inducing TGF-β1 in mice with VMC.