目的 探讨藏药经典方肺热普清散对小鼠肝炎病毒A59（MHV-A59）感染小鼠模型的影响及其对炎症因子的作用。方法 以雄性昆明种小鼠为实验对象，利用 MHV-A59 滴鼻操作建立小鼠冠状病毒感染模型，设置对照组、模型组、阳性（利巴韦林）组和肺热普清散低、中、高剂量（25、50、100 mg·kg^-1）3组，每天ig给药1次，连续给药10 d，考察记录造模期内小鼠体质量变化，处死后称体质量并计算小鼠肺脏指数和肝脏指数；使用Elisa试剂盒测定小鼠血清中炎症因子白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）含量；利用实时荧光定量PCR（qRT-PCR）方法检测小鼠肝脏中IL-1β、IL-18 的mRNA表达水平和血清中MHV-A59病毒载量；通过苏木素-伊红（HE）染色，检测肺热普清散对肝脏和肺脏细胞坏死及炎症细胞浸润的影响。结果 与对照组比较，模型组的体质量增长缓慢（P＜0.01）；肺热普清散 3 个剂量组的体质量每日递增，中、高剂量组在第5～8天均与模型组有显著差异（P＜0.01）；各组小鼠肺脏指数组间无显著性差异，肺热普清散中剂量组肝脏指数与模型组有显著性差异（P＜0.05）；模型组病毒感染后血清中炎症因子 IL-1β 和 IL-18 显著性升高（P＜0.001），与模型组比较，肺热普清散 3个剂量组均可降低血清中 IL-18水平（P＜0.001、0.01）；模型组肝脏组织中 IL-1β和IL-18 的 mRNA 表达水平均显著升高 （P＜0.001）；与模型组比较，肺热普清散高剂量组肝脏中 IL-1β转录水平显著降低（P＜0.01）；与模型组比较，肺热普清散 3组实验动物肝脏组织中 IL-18水平未出现显著性变化；MHV载量测定结果显示，与模型组比较，利巴韦林组和肺热普清散高剂量组血清中MHV载量显著性降低（P＜0.01）；病理切片结果显示，模型组肝脏细胞出现广泛坏死和变性，并出现炎症细胞浸润，气球样变等现象，肺热普清散高剂量和利巴韦林组出现点状病灶、炎症细胞浸润等明显减少现象；模型组肺组织肺泡明显间隔增厚，间质水肿，肺泡被压缩，有炎症细胞浸润，毛细血管扩张充血等现象，而肺热普清散中、高剂量组和阳性组肺组织肺泡间隔较窄，肺泡舒展，局部有炎性浸润和出血，肺泡腔内的分泌物明显减少。结论 肺热普清散对MHV-A59感染小鼠模型具有保护作用，其作用机制与抑制病毒复制和抑制感染后炎症因子有关。

Objective To explore the effects and inflammatory factors of the Tibetan medicine Feire Puqing Powder (FPP) on the mouse model of hepatitis coronavirus A59 (MHV-A59) infection.Methods Male Kunming mice were used as experimental subjects treated with MHV-A59 by nose-dropping, and six groups were set up: the control, the model, the positive (ribavirin), and the FPP's low-, medium-, and high- dosage (25, 50, and 100 mg·kg^-1) groups, and the FPP was ig administered once a day for 10 consecutive days, and the body weight of the mice during the modeling period was examined and recorded, and the lung and liver indices of the mice were examined after execution; The serum levels of IL-1β and IL-18 were determined using the Elisa kit; The mRNA of IL-1β and IL-18 in the liver, and the viral load in the serum were detected using the qRT-PCR; The pathological sections of liver and lung were stained with hematoxylin-eosin (HE), and the necrotic and inflammatory cell infiltration of the liver and lung in each experimental group were observed and recorded under the microscope.Results Compared with the control group, the body weight of the model group increased slowly (P < 0.01); The body weight of the three dose groups of FPP increased daily, and there was a significant difference between middle and high dose groups with the model group on days 5-8 (P < 0.01); There was a significant difference at the liver index of the middle dose group of FPP vs the model group (P < 0.05), while others were no significant difference on the lung index of the mice in each group; The serum inflammatory factors IL-1β and IL-18 were significantly elevated (P < 0.001), and compared with the model group, all three dose groups of FPP reduced the serum level of IL-18, (P < 0.001, 0.01); The IL-1β and IL-18 were significantly elevated in liver tissues of the model group (P < 0.001); Compared with the model group, the transcript level of IL-1β in the liver treated by FPP high-dose group was significantly reduced (P < 0.01); The level of IL-18 in the liver tissues of experimental animals in FPP triple-dose group did not show significant changes; The serum MHV load in each group of mice showed that, compared with the model group, there was a significant reduction of MHV load in the serum in the ribavirin group and the FPP high-dose group (P < 0.01); Liver histopathological sections showed that: Model group showed extensive necrosis and degeneration, with inflammatory cell infiltration and ballooning, while punctate foci and inflammatory cell infiltration were reduced in the FPP high-dose and ribavirin groups; Histopathological sections of lung tissue showed that: lung tissue of the model group showed obvious thickening of alveolar septa, mesenchymal edema, compressed alveoli, with inflammatory cell infiltration, and capillary dilation and congestion, capillary dilatation and congestion, while the alveolar intervals of lung tissues in the middle-dose group, high-dose group and ribavirin group of FPP were narrower, the alveoli were stretched out, and there were still inflammatory infiltration and hemorrhage locally, and secretion in the alveolar lumen was significantly reduced.Conclusion FPP has a protective effect on the MHV-A59 mouse infection, and the mechanism is related to the inhibition of viral replication and the inhibition of inflammatory factor increase.

R29；R51；R37

西藏自治区科技厅科技发展项目（XZ202202YD0020C）；日喀则市区域科技协同创新专项（QYXTZX-RKZ2023-01）