鸢尾苷元磺酸钠对柯萨奇B3型病毒诱导细胞固有免疫的初步研究  

Tectorigenin Sodium Sulfonate Induces Cell-Intrinsic Immunity Against Coxsackie B3 Virus:A Preliminary Study

作　　者：郑晓涵 周静[2] 袁明铭 王媛 张磊 ZHENG Xiaohan;ZHOU Jing;YUAN Mingming;WANG Yuan;ZHANG Lei(School of Pharmacy,Southwest Medical University,Luzhou 646000,China;Sichuan Institute of Chinese Materis Medica,Chengdu 610000,China;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 610000,China)

机构地区：[1]西南医科大学药学院,泸州646000 [2]四川省中医药科学院,成都610000 [3]成都中医药大学药学院,成都610000

出　　处：《病毒学报》2022年第3期534-542,共9页Chinese Journal of Virology

基　　金：四川省科技计划项目(项目号:2020YFS0370),题目:抗病毒中药活性成分评价及关键技术研究与应用。

摘　　要：柯萨奇B组3型(Coxsackievirus B3,CVB3)病毒目前仍严重危害人类健康,目前没有批准的用于CVB3治疗的特效药,亟需开发新的抗CVB3药物。鸢尾苷元磺酸钠(Tectorigenin sodium sulfonate,TSS)是中药川射干化学成分鸢尾苷元的修饰物,本研究应用细胞感染模型评估了TSS体外抗CVB3作用。实验中,以CVB3感染的HT-29细胞为体外模型,在最大无毒浓度(TC0)情况下观察不同浓度药物作用于HT-29细胞后,在72h收集细胞,采用相对荧光定量RT-PCR法检测细胞中CVB3病毒核酸量,TLR3、TRIF mRNA表达水平;收集上清液,采用ELISA法测定上清液NF-κB,TNF-α、IL-6、IFN-β含量。结果显示TSS对HT-29细胞的TC0为15.625μg/mL。与模型组比较,15.625μg/mL剂量的鸢尾苷元磺酸钠能有效增加HT-29细胞活性,降低CVB3病毒滴度(P<0.001),能明显降低细胞内转导和转录活化因子TLR3、TRIF、NF-κB的表达水平(P<0.05),降低炎症因子TNF-α、IL-6、IFN-β的含量(P<0.05)。以上结果表明TSS体外具有显著的抗柯萨奇B3病毒作用,其机制可能是通过调节TLR3/NF-κB免疫信号转导通路而发挥抗病毒作用。Coxsackievirus B3(CVB3)is extremely harmful to human health.Approved specific agents for CVB3 treatment are lacking.There is a great need for the development of anti-CVB3 drugs.Tectorigenin sodium sulfonate(TSS)is a modification of the methoxyisoflavone tectorigenin(a component of the Chinese medicine(TCM)herbal formulation ChuanShegan).We applied a cell-infection model to evaluate the anti-CVB3 effect of TSS in vitro.After treatment of CVB3-infected HT-29 cells with different concentrations of drugs at their maximum non-toxic concentration(TC0),cells were collected at 72 h and the relative amounts of the nucleic acids of CVB3 and mRNA expression of Toll-like receptor(TLR)3 and TLR-like Receptor-associated Interferon Factor(TRIF)were determined by reverse transcription-quantitative polymerase chain reaction.Supernatants were collected,and the content of Nuclear factor-kappa B(NF-κB),Tumor necrosis factor(TNF)-α,Interleukin(IL)-6,and Interferon-βcontent was measured by enzyme-linked immunosorbent assays.The TC0of TSS against HT-29 cells was 15.625μg/mL.Compared with the model group,TSS(15.625μg/mL)increased the viability of HT-29 cells and reduced the CVB3 titer(P<0.001),which significantly reduced expression of the intracellular transducers and transcriptional activators TLR3,TRIF and NF-κB(P<0.05).Expression of the proinflammatory medicators TNF-α,IL-6 and IFN-βwas reduced(P<0.05).Our results indicated that TSS exerts significant anti-CVB3 activity in vitro.The mechanism of action of this antiviral effect may be through regulation of the TLR3/NF-κB signaling pathway.

关 键 词：鸢尾苷元磺酸钠 柯萨奇B3病毒 HT-29细胞 免疫 TLR3/NF-κB信号通路 

分 类 号：R285[医药卫生—中药学] R373.2[医药卫生—中医学]