汉黄芩苷对柯萨奇B3病毒诱导的病毒性心肌炎小鼠炎症反应的影响  

Effect of wogonoside on inflammatory response in mice with viral myocarditis induced by Coxsackie virus B3

作　　者：石哲玮 刘胜新 詹嘉琛 金佳丽 陈莹莹 秦铖璠 钱彩珍 SHI Zhe-wei;LIU Sheng-xin;ZHAN Jia-chen;JIN Jia-li;CHEN Ying-ying;QIN Cheng-fan;QIAN Cai-zhen(Department of Cardiology,Zhuji Hospital Affiliated to Shaoxing University,Shaoxing 311800,China;Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]绍兴文理学院附属诸暨医院心血管内科,浙江诸暨311800 [2]温州医科大学,浙江温州325000

出　　处：《中国病理生理杂志》2020年第3期427-432,共6页Chinese Journal of Pathophysiology

基　　金：浙江省医药卫生科技面上项目(No.2020371419);浙江省医药卫生科技青年人才项目(No.2019329308);绍兴市科技计划项目(No.2018C30148);浙江省医学会科研基金项目(No.2018ZYC-A112);诸暨市科技计划项目(No.2019YW051)。

摘　　要：目的:探讨汉黄芩苷对柯萨奇B3病毒(CVB3)诱导的病毒性心肌炎小鼠炎症反应的影响及其可能的调控机制。方法:用CVB3感染BALB/c小鼠构建病毒性心肌炎动物模型。取40只BALB/c小鼠将其随机分为4组:正常对照组、CVB3感染的病毒性心肌炎组、CVB3感染后给予汉黄芩苷处理的治疗组以及CVB3感染后同时给予汉黄芩苷和AKT激动剂处理的激动剂组,每组10只。于药物治疗7 d后处死各组小鼠。用HE染色检测前3组小鼠心肌组织内炎症细胞浸润情况。用ELISA检测前3组小鼠血清中白细胞介素1β(IL-1β)和IL-6含量。用Western blot实验检测前3组小鼠心脏组织中炎症因子蛋白表达水平以及AKT/NF-κB通路的活化情况。最后,通过Western blot实验检测全部4组小鼠心肺组织中AKT/NF-κB通路的活化情况。结果:与正常组相比,病毒性心肌炎小鼠心脏组织内存在大量炎症细胞浸润,而汉黄芩苷治疗显著降低CVB3病毒诱导的心脏组织炎症细胞浸润(P<0.05)。CVB3病毒感染后小鼠血清中IL-1β和IL-6含量较正常组显著升高(P<0.05),而给予汉黄芩苷治疗后小鼠血清中IL-1β和IL-6含量较病毒性心肌炎组显著降低(P<0.05)。Western blot检测结果表明,与病毒性心肌炎组相比,汉黄芩苷治疗显著降低心肌组织内炎症因子(IL-1β和IL-6)蛋白表达水平以及AKT和NF-κB蛋白的磷酸化水平(P<0.05);而给予AKT激动剂处理后,汉黄芩苷对NF-κB蛋白磷酸化水平的抑制作用显著减弱(P<0.05),且汉黄芩苷对炎症因子的下调作用也显著受到抑制(P<0.05)。结论:汉黄芩苷可通过调控AKT/NF-κB通路减轻病毒性心肌炎小鼠的炎症反应。AIM: To investigate the effect of wogonoside on the inflammatory response of mice with Coxsackie virus B3(CVB3)-induced myocarditis and its possible regulatory mechanism. METHODS: A mouse model of viral myocarditis was constructed by infecting BALB/c mice with CVB3. BALB/c mice(n=40) were randomized into 4 groups: normal group, CVB3-induced viral myocarditis group, CVB3-induced viral myocarditis combined with wogonoside treatment group and CVB3-induced viral myocarditis combined with wogonoside plus AKT agonist treatment group. All the mice were sacrificed 7 days after treatment. In the first 3 groups, HE staining was applied to detect the infiltration of inflammatory cells in the myocardium, ELISA was applied to detect the serum levels of interleukin-1β(IL-1β) and IL-6, while Western blot was applied to detect the protein expression of inflammatory factors and the activation of AKT/NF-κB pathway. Inaddition, the activation of AKT/NF-κB pathway in the 4 groups was detected by Western blot analysis. RESULTS: HE staining showed that there was a large amount of inflammatory cell infiltration in the myocardium of CVB3-induced viral myocarditis mice, as compared with the normal group, which was significantly reduced by wogonoside treatment(P<0.05). The serum levels of IL-1β and IL-6 in the mice after CVB3 infection were significantly higher than those in normal group(P<0.05), which was also significantly reduced by wogonoside treatment(P<0.05). Western blot analysis indicated that wogonoside treatment significantly reduced the expression of inflammatory factors IL-1β and IL-6, and the phosphorylation of AKT/NF-κB pathway-related proteins in the myocardial tissue(P<0.05). After administration of AKT agonist, the inhibitory effect of wogonoside on NF-κB phosphorylation and inflammatory factors expression was significantly eliminated(P<0.05).CONCLUSION: Wogonoside attenuates the inflammatory response of mice with viral myocarditis by inhibiting the AKT/NF-κB pathway.

关 键 词：病毒性心肌炎 汉黄芩苷 AKT/NF-κB信号通路 炎症反应 柯萨奇B3病毒 

分 类 号：R542.21[医药卫生—心血管疾病] R363.2[医药卫生—内科学]