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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(Cox A16)增殖和感染作用的影响。方法分别使用75 TCID_(50)、50 TCID_(50)Cox A16感染Vero细胞模型和5日龄BALB/c乳鼠腹腔内注射1×10~6TCID_(50)Cox A16建立感染动物模型,采用SJM、RBV和SJM+RBV给药后,检测Cox A16感染Vero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Cox A16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Cox A16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Cox A16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Cox A16细胞增殖作用、提高感染Cox A16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Cox A16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 investigate the effects of Sijikangbingdu mixture (SJM), ribavirin injection (RBV) and SJM + RBV on the proliferation and infection of Cox A16 strain. Methods The animal models of infection were established by intraperitoneal injection of 1 × 10 ~ 6 TCID_ (50) Cox A16 in 75 TCID_ (50), 50 TCID_ (50) Cox A16 infected Vero cells and 5 days old BALB / c neonatal mice respectively. After administration of RBV and SJM + RBV, the indexes such as the degree of damage of Vero cells infected with Cox A16 were detected, and the mortality, survival time, body weight, clinical symptom scores and other parameters of the virus infected neonates were calculated. Results SJM, RBV and SJM + RBV significantly inhibited the proliferation of Cox A16 cells in a dose-dependent manner (P <0.01). SJM, RBV and SJM + RBV had significant inhibitory effect on Cox A16 (P <0.01), but SJM + RBV had the strongest inhibitory effect (P <0.01 or P <0.05). Both SJM, RBV and SJM + RBV could significantly improve the clinical symptoms of Cox A16 virus-infected neonatal rats. In particular, the survival rate and clinical score of neonatal rats in SJM + RBV group were significantly better than that of SJM and RBV groups. Conclusion SJM + RBV can inhibit the proliferation of Cox A16 cells and increase the survival rate of Cox A16 virus-infected BALB / c neonatal mice, and prolong the survival time of SJM + RBV. The protective effect of SJM + RBV is better than that of SJM and RBV alone groups, The effective dose of A16 virus (relative to SJM and RBV alone) is a new strategy for the clinical treatment of HFMD.