目的 研究金振口服液抑制小鼠流感病毒性肺炎的藥效及作用機(jī)制。方法 將ICR小鼠隨機(jī)分為對(duì)照組、模型組，金振口服液高、中、低劑量（4.4、2.2、1.1 g/kg）組和磷酸奧司他韋膠囊（0.05 g/kg）組。除對(duì)照組外，其余各組小鼠滴鼻感染甲型H1N1流感病毒構(gòu)建小鼠病毒性肺炎模型，測(cè)定各組小鼠存活時(shí)間和肺指數(shù)；蘇木素–伊紅（HE）染色法觀察肺組織病理變化；流式細(xì)胞術(shù)檢測(cè)外周血CD3⁺、CD4⁺、CD8⁺ T淋巴細(xì)胞水平；ELISA法檢測(cè)血清及肺泡灌洗液中腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1β（IL-1β）、白細(xì)胞介素-6（IL-6）及白細(xì)胞介素-10（IL-10）水平；Western blotting法檢測(cè)肺組織Toll樣受體3（TLR3）、β干擾素TIR結(jié)構(gòu)域銜接蛋白（TRIF）和核轉(zhuǎn)錄因子-κB（NF-κB）蛋白表達(dá)。結(jié)果 與模型組相比，金振口服液給藥組和磷酸奧司他韋膠囊組能顯著延長(zhǎng)小鼠存活時(shí)間，降低肺指數(shù)（P＜0.05、0.01）；減輕肺組織病理?yè)p傷；顯著上調(diào)外周血CD3⁺、CD4⁺ T淋巴細(xì)胞水平及CD4⁺/CD8⁺值，下調(diào)CD8⁺ T淋巴細(xì)胞水平（P＜0.05、0.01）；明顯降低血清及肺泡灌洗液中TNF-α、IL-1β和IL-6水平，升高IL-10水平（P＜0.05、0.01）；顯著抑制肺組織TLR3、TRIF及NF-κB蛋白表達(dá)（P＜0.05、0.01）。結(jié)論 金振口服液能夠延長(zhǎng)病毒性肺炎小鼠存活時(shí)間、降低肺指數(shù)，減輕肺部炎性損傷，其抑制小鼠流感病毒性肺炎的機(jī)制可能與抑制TLR3/TRIF信號(hào)傳導(dǎo)、調(diào)節(jié)抗炎–促炎失衡和改善T細(xì)胞免疫有關(guān)。

Objective To study the efficacy and mechanism of Jinzhen Oral Liquid in inhibiting influenza virus pneumonia in mice. Methods ICR mice were randomly divided into control group, model group, Jinzhen Oral Liquid high, medium, and low dose (4.4, 2.2, 1.1 g/kg) groups, and Oseltamivir Phosphate Capsules (0.05 g/kg) group. Except for the control group, mice in other groups were intranasally infected with influenza A (H1N1) virus to build a mouse viral pneumonia model. Survival time and lung index of mice in each group were measured. The pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The levels of CD3⁺, CD4⁺, CD8⁺T lymphocytes in peripheral blood were detected by flow cytometry. Detection of TNF-α, IL-1β, IL-6, and IL-10 levels in serum and alveolar lavage fluid were carried out by ELISA. Western blotting method was used to detect TLR3, TRIF, and NF-κB protein expression. Results Compared with the model group, the survival time of mice in Jinzhen Oral Liquid group and Oseltamivir Phosphate Capsules group were significantly prolonged, and the lung index was reduced (P < 0.05, 0.01). The pathological results also showed alleviated damage of lung tissue in these two groups. The level of CD3⁺, CD4⁺ T lymphocytes and the ratio of CD4⁺/CD8⁺ in peripheral blood were largely increased, and the level of CD8⁺T lymphocytes was greatly decreased (P < 0.05, 0.01). TNF-α, IL-1β and IL-6 content in serum and alveolar lavage fluid were reduced, while IL-10 content was increased (P < 0.05, 0.01). The expression of TLR3, TRIF, and NF-κB were significantly inhibited in lung tissue (P < 0.05, 0.01). Conclusion Jinzhen Oral Liquid can prolong the survival time of mice with viral pneumonia, reduce lung index, and alleviate lung inflammatory injury. Its mechanism of inhibiting influenza viral pneumonia in mice may be related to the inhibition of TLR3/TRIF signal transduction, regulation of anti-inflammatory and pro-inflammatory imbalance, and improvement of T cell immunity.

R285.5

國(guó)家中醫(yī)藥管理局青年岐黃學(xué)者項(xiàng)目（國(guó)中醫(yī)藥人教函〔2022〕6號(hào)）；國(guó)家中醫(yī)藥管理局交叉創(chuàng)新團(tuán)隊(duì)項(xiàng)目（ZYYCXTU-D-202203）