【摘要】 目的 通过建立人冠状病毒229E湿热疫毒袭肺小鼠模型，模拟新型冠状病毒感染的中医症候，观察预防给予清解防感颗粒对该病症结合小鼠模型的作用，探索其对新型冠状病毒感染的可能作用。方法 60只BALB/C小鼠，随机分为正常组、湿毒组、湿热组、病毒组、清解防感颗粒高/低剂量组(8.2/4.1 g·kg^-1·d^-1)，采用湿热环境和229E滴鼻感染小鼠造模，建立人冠状病毒229E湿热疫毒袭肺病症结合小鼠模型，给药组从小鼠放入湿热环境时开始给药，直至229E病毒感染前，229E病毒感染后第2天解剖小鼠，摘取肺脏、脾脏。计算肺脏、脾脏指数及肺抑制率，RTPCR法检测肺组织病毒载量，并检测肺脏、脾脏病理情况，ELISA检测肺组织中炎症因子IL-6、TNF-α、IL-1β及IL-8的含量水平。WB法检测肺组织中MAPK信号通路中P-p38、p38蛋白的表达量。结果 与湿毒组比较，清解防感颗粒显著降低人冠状病毒229E湿热疫毒袭肺小鼠肺指数（P<0.01）；升高脾指数（P<0.05），高、低剂量组肺指数抑制率分别为61.73%和71.15%；能够显著降低肺组织病毒载量（P<0.01）、减轻肺组织病变（P<0.01或P<0.05），改善脾组织病理改变；显著降低小鼠肺组织中IL-6、TNF-α、IL-1β及IL-8的含量水平（P<0.01或P<0.05）及MAPK通路中P-p38蛋白表达（P<0.05）。结论 预防给予清解防感颗粒，能够减轻人冠状病毒229E湿热疫毒袭肺模型小鼠肺部炎症，其作用机制可能与抑制p38蛋白磷酸化及MAPK通路有关。更多还原

【Abstract】 Objective To observe the effect of preventive administration of Qingjie Fanggan Granules on this disease-model combination, and explore its possible role in COVID-19 by establishing a mouse model of human coronavirus 229E infection with dampness-heat pestilential toxin attacking the lung, which simulates the TCM syndromes of COVID-19 infection. Methods Sixty BALB/C mice were randomly divided into normal control group, dampness-toxin control group, dampnessheat control group, virus control group, and high/low dose groups of Qingjie Fanggan Granules(8.2/4.1 g·kg^-1·d^-1). The syndrome-combined model of human coronavirus 229E was established by modeling mice with a damp-heat environment and intranasal infection of 229E. The administration groups were given the drug starting from when the mice were placed in the damp-heat environment until before 229E virus infection. Mice were sacrificed 1 day after 229E virus infection, and lungs and spleens were harvested. Calculate lung and spleen indices, lung inhibition rate. Detect viral load in lung tissues by RT-PCR, observe pathological changes of lung and spleen. Detect levels of inflammatory factors IL-6, TNF-α, IL-1β and IL-8 in lung tissues by ELISA. Detect expressions of P-p38 and p38 proteins in p38 MAPK signaling pathway of lung tissues by Western Blot. Results Compared with the dampness-toxin control group, Qingjie Fanggan Granules significantly reduced the lung index（P<0.01） and increased the spleen index（P<0.05） in mice with damp-heat pestilential toxin attacking the lung infected by human coronavirus 229E. The lung index inhibition rates of high and low-dose groups were 61.73% and 71.15% respectively. It could significantly reduce the viral load in lung tissues（P<0.01）, alleviate lung tissue lesions（P<0.01 or P<0.05）, improve splenic tissue pathological changes, and significantly decrease the levels of IL-6, TNF-α, IL-1β and IL-8 in lung tissues（P<0.01 or P<0.05）, as well as the expression of P-p38 protein in the MAPK pathway（P<0.05）. Conclusion Preventive administration of Qingjie Fanggan Granules can alleviate lung inflammation caused by HCo V-229E infection, and its mechanism may be related to the inhibition of p38 protein phosphorylation and the MAPK signaling pathway.更多还原