穿心莲内酯对柯萨奇病毒A16感染长爪沙鼠的保护作用  

Protective effect of andrographolide on coxsackievirus A16 infection in Mongolian gerbils

作　　者：陈童画 罗立君 张锋 唐彩华 罗永能 高丽美 Chen Tonghud;Luo Lijun;Zhang Feng;Tang Caihud;Luo Yongneng;Gao Limei(School of Information Engineering,Hangzhou Medical College,Hangzhou 311399,China;School of Pharmacy,Hangzhou Medical College,Hangzhou 311399,China;School of Clinical Medicine,Hangzhou Medical College,Hangzhou 311399,China;School of Basic and Forensic Medicine,Hangzhou Medical College,Hangzhou 311399,China;School of Laboratory Medicine,Hangzhou Medical College,Hangzhou 311399,China)

机构地区：[1]杭州医学院信息工程学院,杭州311399 [2]杭州医学院药学院,杭州311399 [3]杭州医学院临床医学院,杭州311399 [4]杭州医学院基础医学与法医学院,杭州311399 [5]杭州医学院检验医学院,杭州311399

出　　处：《国际流行病学传染病学杂志》2024年第5期321-327,共7页International Journal of Epidemiology and Infectious Disease

基　　金：国家级大学生创新创业训练计划项目(202313023025)。

摘　　要：目的探讨穿心莲内酯对柯萨奇病毒A16型(coxsackievirus A16,CA16)感染长爪沙鼠的保护作用。方法取40只14日龄的长爪沙鼠,10只作为正常对照组(C组)不进行病毒干预和腹腔注射;30只通过腹腔注射1.0×10^(5)CCID50剂量CA16建立感染模型沙鼠,随机分成模型对照组(M组,生理盐水)、利巴韦林组(R组,12.5 mg·kg^(-1)·d^(-1))、穿心莲内酯组(A组,15 mg·kg^(-1)·d^(-1)),每组10只,1次/d腹腔注射,连续给药7 d。治疗过程中观察沙鼠临床症状和存活情况。治疗7 d后,取组织免疫组化检测,应用实时荧光定量qPCR和Western印迹法分别检测组织中TNF-α、IL-1β、IL-6、TLR4和NF-κB p65的mRNA和蛋白表达水平。结果A组沙鼠临床评分为13分,高于M组。7 d治疗后,A组中共4只小鼠生存,不同组间比较差异有统计学意义(χ^(2)=18.06,P=0.001)。A组肠道、肌肉和脑组织中TNF-α、IL-1β、IL-6、NF-κB p65和TLR4的mRNA和蛋白表达水平较M组降低(t=311.79、114.47、28.17、273.47、289.52、150.84、169.70、319.47、235.55、24.01、13.64、127.41、436.25、113.04和65.46,P<0.001、<0.001、<0.001、<0.001、<0.001、<0.001、<0.001、<0.001、<0.001、=0.027、=0.005、<0.001、<0.001、<0.001和<0.001)。结论穿心莲内酯对CA16感染具有抗病毒作用,其机制与抑制TLR4/NF-κB的信号通路活化和抗炎相关。Objective:To investigate the protective effect of andrographolide(Andro)on coxsackievirus A16(CA16)infection in Mongolian gerbils.Methods:A total of 4014-day-old Mongolian gerbils were used,among which 10 mice were used as normal control group(group C)without virus intervention or intraperitoneal injection.The rest 30 mice were injected intraperitoneally with CA16(1.0×10^(5) CCID50 dose)to establish an infection model of gerbils.Then,they were randomly divided into a model control group(group M,physiological saline),a ribavirin group(group R,ribavirin 12.5 mg·kg^(-1)·d^(-1)),and an Andro group(group A,Andro 15 mg·kg^(-1)·d^(-1)),with 10 gerbils in each group.They were injected intraperitoneally once a day and administered continuously for 7 days.The clinical symptoms and survival of gerbils were monitored during the treatment.After 7 days of treatment,the tissue was taken for immunohistochemical detection.RT-qPCR and Western blot were used to detect mRNA and protein levels of TNF-α,IL-1β,IL-6,TLR4 and NF-κB p65.Results:Compared with group M,group A showed significant improvement in clinical symptoms with clinical score of 13.After 7-day treatment,the survival rates had significantly different among different groups(χ^(2)=18.06,P=0.001),with group A having 4 surviving mice.The mRNA and protein levels of TNF-α,IL-1β,IL-6,TLR4 and NF-κB p65 in the intestine,muscle and brain tissue of group A were significantly lower than those in group M(t=311.79,114.47,28.17,273.47,289.52,150.84,169.70,319.47,235.55,24.01,13.64,127.41,436.25,113.04和65.46,P<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,=0.027,=0.005,<0.001,<0.001,<0.001和<0.001).Conclusions:Andro has antiviral effects against CA16,possibly by inhibiting the TLR4/NF-κB signaling pathway activation and associated anti-inflammatory mechanisms.

关 键 词：穿心莲内酯 柯萨奇病毒A16 手足口病 沙鼠 随机对照试验 

分 类 号：R285.5[医药卫生—中药学]