目的：探讨白介素（IL）-23/IL-17信号通路在病毒性心肌炎（VMC）中的作用及黄芪甲苷的干预效果。方法将75只雄性BALB/c小鼠随机分为对照组（n=15）、模型组（n=20）、低剂量干预组（n=20）及高剂量干预组（n=20），对照组小鼠腹腔注射0.1 ml病毒培养液，其余三组腹腔接种0.1 ml含1×102 TCID50柯萨奇病毒B3培养液建立VMC模型。接种后当日，低、高剂量干预组分别以1%、9%黄芪甲苷0.1 ml灌胃，对照组、模型组以0.1 ml羧甲基纤维素钠溶液灌胃，每天1次，共14 d。期间观察各组表现及死亡情况。第15天处死小鼠取心脏及血液标本，HE染色计算心肌病理积分，流式细胞术分析Th17细胞频率，荧光实时定量PCR、Western blotting检测心肌IL-23、IL-17 mRNA及蛋白表达。结果四组间死亡率差异有统计学意义（P=0.013），对照组死亡率最低。高剂量干预组的心肌病理积分、Th17细胞频率、心肌IL-23和IL-17 mRNA与蛋白表达水平均低于模型组和低剂量干预组，但高于对照组，差异有统计学意义（P均<0.05）；模型组和低剂量干预组均高于对照组，差异有统计学意义（P均<0.05），而模型组和低剂量干预组之间差异无统计学意义（P>0.05）。结论黄芪甲苷可能通过抑制IL-23/IL-17信号通路发挥抗VMC作用，且具有剂量依赖性。%Objective To explore the role of interleukin-23 (IL-23)/interleukin-17 (IL-17) signaling pathway in viral myocarditis (VMC) and evaluate the intervention effect of Aastragaloside. Methods Seventy-five male BALB/c mice were randomly divided into 4 groups, control group (n=15), model group (n=20), low-dose intervention group (n=20) and high-dose intervention group (n=20). Mice in control group were inoculated with 0.1 ml virus cultivation solution intraperitoneally while mice in the other 3 groups were treated with 0.1ml virus cultivation solution containing 1×102 TCID50 coxsackievirus B3 (CVB3) to establish VMC model. On the day of inoculation, mice in low- and high-dose intervention groups were intra-gastrically administered with 0.1 ml of 1% and 9%Astragaloside solution respectively, whereas those in control and model groups were treated with 0.1 ml carboxymethycellulose solution. Astragaloside or carboxymethycellulose was given once a day and continued 15 days. The number of mice death and the performance of mice were recorded in experimental period. All mice were sacrificed on day 15. The heart and blood sample were obtained. Histological cross sections of heart were stained with hematoxylin-eosin and scored for myocardial histopathologic changes under optical microscope. Th17 cells were analyzed by flow cytometry. The mRNA and protein expression levels of myocardial IL-23 and IL-17 were detected by real-time quantitative PCR and Western blotting, respectively. Results The mortality was statistically significant differ-ences among the four groups (P= 0.013), which was the lowest in the control group. The myocardial histopathologic scores, the percen-tage of Th17 cells, as well as expression levels of myocardial IL-23 and IL-17 mRNA and protein were significantly lower in high-dose intervention group than those in model group and low-dose intervention group, but higher than those in control group (P < 0.05). The myocardial histopathologic scores, the percentage of Th17 cells, as well as ex-pression levels of myocardial IL-23 and IL-17 mRNA and protein were significantly higher in model group and low-dose in-tervention group (P < 0.05). There were no significant difference in the above mentioned indicators between low-dose inter-vention group and model group (P > 0.05). Conclusions Astragaloside may dose-dependently protect against VMC by in-hibiting IL-23/IL-17 signaling pathway.
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