小儿热速清糖浆防治手足口病的体内外药效学研究

Pharmacodynamics Research on the Preventive and Therapeutic Effects of Xiaoer Resuqing Syrup on Hand,Foot and Mouth Disease

手足口病(Hand,foot and mouth disease,HFMD)是由肠道病毒感染引起的一种儿童常见传染病,全球普遍高发,严重威胁患儿健康。目前缺乏有效治疗药物,主要进行对症治疗,因此,研发高效的抗HFMD相关肠道病毒的药物和治疗方法十分重要。本研究应用细胞和小动物感染模型评价了小儿热速清糖浆(RSQ)对肠道病毒A组71型(Enterovirus A71,EV-A71)致病能力的抑制作用。体内实验中,小儿热速清糖浆设计66ml/(kg·d^(-1))、33ml/(kg·d^(-1))、16.5ml/(kg·d^(-1))三个剂量组,分别对EV-A71 H株感染的BALB/c乳鼠进行预防性和治疗性给药,观察乳鼠感染的严重程度及死亡数、动物死亡率、死亡保护率以及生命延长率。体外实验中,采用CPE法观察小儿热速清糖浆对EV-A71 H株、EV-A71 BrCr株、柯萨奇病毒(Coxsackievirus,Cox)B_3株、Cox B_4株、Cox B_5株所致细胞病变的抑制作用。体内试验结果显示,预防性和治疗性给予小儿热速清糖浆后,中、小剂量组乳鼠的感染程度积分及死亡率均明显降低,并可以延长动物的存活时间,大剂量组未表现出明显的药效作用。体外实验结果显示,小儿热速清糖浆对EV-A71 H株、Cox B_5株、EV-A71 BrCr株及Cox B_3株所致RD或Hep-2细胞病变具有一定的抑制作用,治疗指数分别为5.77、5.01、3.98、2.30。以上结果表明,小儿热速清糖浆对EV-A71 H株感染的手足口病乳鼠模型具有显著的预防和治疗作用,在体外对手足口病致病病毒EV-A71 H株、EV-A71 BrCr株、Cox B_3及Cox B_5株均有明显的抑制作用。

Hand,foot and mouth disease(HFMD)was a common infectious disease caused by enterovirus infection.It was widespread in the world and threatened the health of children.At present,there was no effective treatments,so it was important to develop high-efficiency drugs and treatments related to HFMD.In this study,the cell and small animal infection models were used to evaluate the inhibitory effect of Xiaoer Resuqing syrup(RSQ)on the pathogenicity of Enterovirus A71(EV-A71).In the experiment in vivo,three dose groups(66,33,16.5 ml/(kg·d^(-1)))were designed.Prophylactic and therapeutic administration of RSQ was applied to mice infected with EV-A71 H strain.We observed the degree of infection,mortality and survival.In the experiment in vitro,inhibition by RSQ at five non-toxic doses of EV-A71 H as well as EV-A71 Brcr,Coxsackievirus(Cox)B3,Cox B4 and Cox B5 strains was determined by the cytopathogenic-effect method on Hep-2 or RD cells.The results showed that medium and low-dose groups of RSQ could reduce the degree of infection and mortality,and simultaneously increase survival significantly.RSQ showed significant preventive and therapeutic effects on suckling BALB/c mice infected with EV-A71 H strain.At no-toxic doses,RSQ inhibited infection with EV-A71 H as well as that by EV-A71 Brcr,Cox B3 and Cox B5 strains visibly,and the therapeutic index was 5.77,5.01,3.98 and 2.30,respectively.The results indicated that RSQ has a good pharmacologic effect against HFMD due to EV-A71 H strain infection in vivo,and has strong effects against HFMD due to infection with EV-A71 H,EV-A71 BrCr,Cox B5 and Cox B3 strains in vitro.