大黄素对病毒性心肌炎小鼠IL-23/IL-17炎症轴、Th17细胞及病毒复制的影响  

Effects of emodin on IL-23/IL-17 inflammatory axis, Th17 cells and viral replication in mice with viral myocarditis

作　　者：蒋娜[1] 廖雯婷[2] 匡希斌[1] 

机构地区：[1]南华大学附属第二医院,湖南衡阳421001 [2]南方医科大学病理学系,广东广州510515

出　　处：《南方医科大学学报》2014年第3期373-378,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(81172055)~~

摘　　要：目的探讨大黄素对病毒性心肌炎(VMC)小鼠心肌的保护作用及其分子机制。方法 55只雄性BALB/c小鼠随机分为对照组(n=15)、模型组(n=20)及大黄素组(n=20),模型组、大黄素组小鼠腹腔接种0.1 ml内含柯萨奇病毒B3(CVB3)的Eagle's液建立VMC模型,对照组仅注射Eagle’s液,于接种当天,大黄素组以3 mg/ml大黄素溶液0.1 ml灌胃,其余2组以0.1 ml蒸馏水灌胃,1次/d,共21 d,记录实验期间小鼠死亡数目,比较各组死亡率。第7天每组处死5只小鼠,取心脏,测定病毒滴度。第22天称体质量(BW)后处死全部小鼠,收集外周血,剥离心脏,称心脏质量(HW),计算HW/BW,行HE染色计算心肌病理积分,采用荧光实时定量PCR、Western blotting分别检测心肌白介素-23(IL-23)、白介素-17(IL-17)mRNA和蛋白表达,通过酶联免疫吸附法测定血清IL-23、IL-17浓度,流式细胞术分析Th17细胞频率,利用Western blotting测定心肌细胞核内核因子-κB(NF-κB)p65表达,ELISA分析心肌白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量。结果大黄素组死亡率、心肌病理积分及病毒滴度较模型组减少(P<0.05)。模型组HW/BW、心肌IL-23及IL-17 mRNA与蛋白表达水平、血清IL-23和IL-17浓度、Th17细胞频率、胞核NF-κB p65表达水平及心肌IL-1β、IL-6、TNF-α含量显著高于对照组(P<0.01),与模型组比较,大黄素组上述指标明显降低(P<0.05)。结论大黄素可能通过抑制IL-23/IL-17炎症轴、Th17细胞增殖及病毒复制发挥抗VMC作用。Objective To explore the effects of emodin in myocardial protection in mice with viral myocarditis （VMC） and explore molecular mechanisms. Methods Fifty-five male 4-week-old BALB/c mice were randomly divided into control group （n=15）, model group （n=20）, and emodin group （n=20）. The mice in model and emodin groups were inoculated with 0.1 ml Eagle＆#39;s solution containing coxsackievirus B3 intraperitoneally, and those in the control group were given only 0.1 ml Eagle＆#39;s solution. From the day of inoculation, the mice in emodin group received intragastric administration with 0.1 ml of 3 mg/ml emodin solution once daily for 21 consecutive days, and those in the control and model groups received 0.1 ml distilled water only. On day 7 after inoculation, 5 mice from each group were sacrificed to determine the viral titers in the cardiac tissues. All the mice were sacrificed on day 22 for measurement of the heart weight and histopathological inspection of the heart with HE staining. The mRNA and protein expression levels of myocardial interleukin-23 （IL-23） and interleukin-17 （IL-17） were detected by real-time quantitative PCR and Western blotting, respectively, and serum IL-23 and IL-17 levels were examined using enzyme linked immunosorbent assay （ELISA）. Th17 cell frequencies were analyzed by flow cytometry. The expression levels of myocardial nuclear factor-κB （NF-κB） p65 in the cardiomyocyte nuclei were examined using Western blotting, and myocardial interleukin （IL）-1β, IL-6 and tumor necrosis factor-α （TNF-α） contents were detected by ELISA. Results The mortality, myocardial histopathologic scores and virus titers in emodin group were all significantly lower than those in the model group （P＆lt;0.05）. The heart-to-body weight ratio, myocardial IL-23 and IL-17 expressions, serum IL-23 and IL-17 levels, Th17 cell frequencies, cardiomyocyte nuclear NF-κB p65 expression, and myocardial contents of IL-1β, IL-6 and TNF-αwere all significantly increased in the

关 键 词：大黄素 病毒性心肌炎 白介素-23 白介素-17 TH17细胞 INTERLEUKIN-23 INTERLEUKIN-17 

分 类 号：R285.5[医药卫生—中药学]