盐酸石蒜碱硫酯体内抗柯萨奇病毒A16的药效研究  

Efficacy of lycorine thioester hydrochloride against coxsackievirus A16 in vivo

作　　者：王辉强[1,2] 颜海燕 李兴琼[1,2] 杨杰 李玉环[1,2] WANG Huiqiang;YAN Haiyan;LI Xingqiong;YANG Jie;LI Yuhuan(Key Laboratory of Antiviral Drugs,Chinese Academy of Medical Sciences,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Beijing Key Laboratory of Anti-Infective Drugs,Institute of Medicinal Biotechnology,Chinese Acade­my of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Shandong DYNE Marine Biopharmaceutical Co.,Ltd.,Rongcheng Shandong 264300,China)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,中国医学科学院抗病毒药物研究重点实验室,北京100050 [2]中国医学科学院北京协和医学院医药生物技术研究所,抗感染药物研究北京市重点实验室,北京100050 [3]山东达因海洋生物制药股份有限公司,山东荣成264300

出　　处：《中国药物警戒》2023年第1期79-84,共6页Chinese Journal of Pharmacovigilance

基　　金：国家科技重大专项重大新药创制(2018ZX09721003-008-026);中国医学科学院医学与健康科技创新工程(2021-1-I2M-030)。

摘　　要：目的研究盐酸石蒜碱硫酯在体内抗柯萨奇病毒A16(CVA16)的药效。方法通过腹腔注射病毒液方式感染10~11 d的ICR小鼠建立CVA16感染的小鼠模型。实验分为盐酸石蒜碱硫酯1.0、0.5、0.25 mg·kg^(-1)组;50 mg·kg^(-1)RBV对照组;病毒对照组;正常对照组。检测盐酸石蒜碱硫酯对病毒感染后小鼠发病情况、小鼠存活率和平均存活日;蛋白免疫印迹法(Western-blot)检测肌肉组织中病毒蛋白的表达水平;采用细胞病变效应法(CPE)测定肌肉组织中的病毒滴度;采用苏木素伊红(HE)染色检测肌肉组织的病理变化。结果与病毒对照组相比,盐酸石蒜碱硫酯1.0和0.5 mg·kg^(-1)剂量组能够显著降低小鼠肌肉组织的病毒滴度和病毒蛋白表达,降低CVA16感染造成的小鼠肌肉组织的炎症损伤,延缓小鼠的发病过程,显著延长小鼠的平均存活时间,增加小鼠的存活率,具有明确的保护作用。结论盐酸石蒜碱硫酯1.0和0.5 mg·kg^(-1)剂量组对CVA16感染小鼠具有显著明确的保护作用,提示盐酸石蒜碱硫酯可能成为潜在的治疗手足口病的药物。Objective To investigate the efficacy of lycorine thioester hydrochloride against coxsackievirus A16(CVA16)in vivo.Methods A mouse model of CVA16 infection was established via intraperitoneal injection of CVA16 in ICR mice aged 10 to 11 days.The experimental groups were divided into 1.0,0.5 and 0.25 mg·kg^(-1)lycorine thioester hydrochloride groups,50 mg·kg^(-1)RBV control group,virus control group,and the normal control group.The incidence of infections,survival rate and average survival of mice after virus infection were detected.The expression level of the viral protein in muscle tissue was detected by Western-blot assay.Cytopathic effect assay(CPE)was used to detect the viral titer in muscle tissue.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of muscle tissue.Results Compared with the virus control group,administration of lycorine thioester hydrochloride 1.0 and 0.5 mg·kg^(-1)could significantly reduce the viral titer and viral protein expression in muscle tissue,mitigate the inflammatory injury caused by CVA16 infection,delay the pathogenesis of mice,significantly prolong the average survival of mice,and increase the survival rate of mice.Conclusion Administration of lycorine thioester hydrochloride 1.0 and 0.5 mg·kg^(-1)has a significant protective effect on CVA16-infected mice,suggesting that lycorine thioester hydrochloride may be a potential drug for the treatment of hand,foot,and mouth disease(HFMD).

关 键 词：盐酸石蒜碱硫酯 柯萨奇病毒A16 手足口病 体内抗病毒药效 小鼠 

分 类 号：R917[医药卫生—药物分析学] R978.7[医药卫生—药学]