四季抗病毒合剂联用利巴韦林对CoxA16病毒增殖和感染作用的影响

Study on Sijikangbingdu Mixture and Ribavirin Injection in Inhibiting CoxA16 Viruses Proliferation and Infection

目的探讨四季抗病毒合剂（Sijikangbingdu mixture，SJM）、利巴韦林注射液（Ribavirin injection，RBV）和SJM＋RBV对A16型柯萨奇病毒（CoxAl6）增殖和感染作用的影响。方法分别使用75TCID5、50TCID50CoxAl6感染Vero细胞模型和5日龄BALB／c乳鼠腹腔内注射1×10^6TCID50CoxAl6建立感染动物模型，采用SJM、RBV和SJM＋RBV给药后，检测CoxAl6感染Veto细胞损伤程度等指标，计算各用药方式对病毒感染乳鼠的死亡率、生存时间、体质量、临床症状评分等参数。结果SJM、RBV和SJM＋RBV对CoxAl6细胞的增殖具有剂量依赖性显著抑制作用，即随其剂量增大抑制作用显著增强（P〈0．01）。SJM、RBV和SJM＋RBV对CoxAl6病毒均具有显著抑制作用（P〈0．01），但SJM＋RBV组的抑制作用最强（P〈0．01或P〈0．05）。SJM、RBV和SJM＋RBV均能显著改善CoxAl6病毒感染乳鼠的临床症状，尤其SJM＋RBV组的乳鼠生存率和临床评分等指标均显著好于SJM和RBV组。结论SJM＋RBV抑制CoxAl6细胞增殖作用、提高感染CoxAl6病毒BALB／c乳鼠的存活率、延长其存活时间等保护效应均显著优于SJM、RBV单用组，并显著下移了抗CoxAl6病毒的有效剂量（相对SJM、RBV单用有效剂量而言），为临床治疗手足口病提供了用药新策略。

Objective To study the antiviral effects of Sijikangbingdu mixture （SJM） ,Ribavirin injection（RBV） and SJM ＋ RBV a- gainst coxsackievirus A16 （ CoxA16）. Methods We established a Vero cell model respectively injected with 75 and 50 TCIDs0 CoxA16, and a suckling mice animal model of infection respectively injected with ip 1 × 10^6 TCIDso CoxA16. Using the degree of injury of Vero cells infected by CoxAl6 and using the mortality, survival time, change rate of body weight, and clinical symptom scores of suckling mice,we evaluated the effect of SJM, RBV and SJM ＋ RBV, after administrating SJM,RBV and SJM ＋ RBV, respectively. Results The inhibition activity of SJM, RBV and SJM ＋ RBV for the proliferation of CoxA16 had a dose - dependent relationship,and the their inhibition activity increased with doses increasing（P 〈 O. 01 ）. But The inhibitory effect of SJM ＋ RBV was the strongest （ P 〈 0. O1 or P 〈 0.05 ）. SJM, RBV and SJM ＋ RBV can significantly improve the clinical symptoms of CoxA16 virus infected mice, especially in the SJM ＋ RBV. The survival rate and clinical score were significantly better than SJM and RBV. Conclusion The effect of SJM ＋ RBV in inhibiting CoxA16 cell proliferation, improving infected BALB/c mice＇s survival rate and prolonging their survival time etc. was significantly superior to SJM and RBV, and it significantly reduced the antiCox A15 virus effective doses （for SJM and RBV single effective dose） ,so it provides a new clinical treatment strategy for the hand - foot - mouth disease.