目的 研究银花青蒿栀子方灌肠剂体内抗A6型柯萨奇病毒（coxsavirus A6，CV-A6）的作用及机制。方法 10 d龄ICR乳鼠随机分为对照组、模型组、银花青蒿栀子方灌肠剂（2.6 g/kg）组和利巴韦林（10 mg/kg）组，除对照组外，其余各组ip滴度为10^7.4 TCID₅₀/mL的CV-A6感染；给予药物进行干预，考察银花青蒿栀子方灌肠剂对CV-A6感染的乳鼠血清中细胞因子水平、组织病毒载量、生存率、临床评分、组织病理变化、脊髓颈膨大段超微结构和骨骼肌细胞凋亡的影响。结果 与模型组比较，银花青蒿栀子方灌肠剂组乳鼠血清中白细胞介素-5（interleukin 5，IL-5）、IL-6、IL-12 p70、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、γ干扰素（interferon-γ，IFN-γ）和转化生长因子-β（transforming growth factor-β，TGF-β）水平均显著降低（P<0.01、0.001），心脏、肺脏、脊髓、延髓和后肢骨骼肌组织病毒载量均显著降低（P<0.05、0.01），乳鼠生存率提高，急性弛缓性麻痹等症状明显缓解，骨骼肌、心脏、肺脏等组织的病理损伤和脊髓前角神经元损伤减轻，骨骼肌细胞凋亡减少。结论 银花青蒿栀子方灌肠剂在ICR乳鼠体内具有良好的抗CV-A6作用，可能与保护脊髓前角神经元、抑制细胞凋亡、减轻细胞因子风暴等有关。

Objective To explore the effect and mechanisms action of Yinhua-Qinghao-Zhizi Enema (银花青蒿栀子方灌肠剂, YQZE) against coxsackievirus A6 (CV-A6) in vivo. Methods Ten-day-old ICR mice were divided into control group, model group, YQZE (2.6 g/kg) group and ribavirin (10 mg/kg) group. Except control group, others were ip 10^7.4 TCID₅₀/mL CV-A6. Drugs were given to intervene to investigate the effect of YQZE on levels of cytokine concentration in serum, virus load in tissues, survival rate, clinical score, pathological changes, ultrastructure of cervical myelopathy, and cell apoptosis of skeletal muscle in mice. Results Compared with model group, levels of interleukin 5 (IL-5), IL-6, IL-12 p70, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β) in serum of YQZE group were significantly reduced (P < 0.01, 0.001); Virus load in heart, lungs, spinal cord, medulla oblongata and hind limb skeletal muscle tissues were significantly reduced (P < 0.05, 0.01); Survival rate was improved and symptoms such as acute flaccid paralysis were relieved; Pathological injuries of tissues and damage of neurons in anterior horn were relieved; Skeletal muscle cell apoptosis rate was decreased. Conclusion YQZE has significant anti-CV-A6 effect in ICR mice, which may be related with protection of neurons in anterior horn, inhibition of cell apoptosis and cytokine storm.

R285.5

山东省重点研发计划项目（2017GSF19106）；山东省中医药科技发展计划项目（2017-248）；山东省自然科学基金资助项目（ZR2018PH034）；山东第一医科大学学术提升计划项目（2019LJ003）