目的 表征麻黄细辛附子汤（Mahuang Xixin Fuzi Decoction，MXF）和麻黄甘草附子汤（Mahuang Gancao Fuzi Decoction，MGF）的物质基础，探究MXF、MGF对肾阳虚外感证小鼠模型的干预作用差异及其作用机制，为临床精准用药提供基础研究依据。方法 运用超高效液相色谱-三重四极杆质谱（UPLC-QQQ/MS）对MXF与MGF化学成分进行分析。将60只BALB/c小鼠随机分为对照组（12只）和肾阳虚证模型组（48只）。通过ip苯甲酸雌二醇复制肾阳虚证小鼠模型，在此基础上滴鼻感染H1N1流感病毒，建立肾阳虚外感证小鼠模型。将造模成功的小鼠随机分为模型组、MXF（1.8 g/kg）组、MGF（1.8 g/kg）组和奥司他韦（22.53 mg/kg）组，每组12只。连续给药7 d，检测各组小鼠体质量、肛温、生存率、脏器指数、肺组织病理、气管和肺泡灌洗液分泌型免疫球蛋白A（secretory immunoglobulin A，SIgA）水平、肺部病毒载量及血清炎性细胞因子水平的变化。结果 从MXF中检测到麻黄碱类、乌头碱及芝麻酯素、细辛脂素等15种成分，从MGF中检测到麻黄碱类、乌头碱及甘草苷等18种成分，MXF中所含的麻黄类生物碱成分高于MGF。与模型组比较，各给药组均可恢复小鼠体质量、肛温，恢复效果奥司他韦＞MXF＞MGF；奥司他韦、MXF组无小鼠死亡，MGF组有1只小鼠死亡；奥司他韦组和MXF组肺指数显著降低（P＜0.05、0.01）；各给药组小鼠肺组织病变减轻，减轻程度奥司他韦＞MXF＞MGF；MXF对小鼠肺部病毒的清除率更高；MGF显著升高肺部灌洗液中SIgA水平（P＜0.05）；奥司他韦、MXF、MGF均能有效降低促炎因子与抗炎因子总值、促炎因子与抗炎因子比值和促炎因子比例，减轻机体炎症反应，且MGF抗炎及免疫增强作用高于MXF；通过综合疗效的箱式图分析可知MXF优于MGF。结论MXF和MGF中不同的佐药（细辛/甘草）影响了方中共有成分（麻黄类生物碱、附子类生物碱）的含量；MXF与MGF均能有效治疗肾阳虚外感证，减轻病毒感染后对机体造成的损伤。二者比较，MXF的综合药效作用较好，但MGF对炎症因子及免疫调控的作用更优。

Objective To characterize the material basis of Mahuang Xixin Fuzi Decoction (麻黄细辛附子汤, MXF) and Mahuang Gancao Fuzi Decoction (麻黄甘草附子汤, MGF), and explore the differences in intervention effects and mechanisms of MXF and MGF on mouse models of kidney-yang deficiency and external infection syndrome, and provide basic research basis for clinical precision medication. Methods The chemical composition of MXF and MGF was analyzed using ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ/MS). A total of 60 BALB/c mice were randomly divided into control group (12 mice) and kidney-yang deficiency syndrome model group (48 mice). A mouse model of kidney-yang deficiency syndrome was established by ip estradiol benzoate, and then intranasal infection with H1N1 influenza virus was performed to establish a mouse model of kidney-yang deficiency and external infection syndrome. The successfully modeled mice were randomly divided into model group, MXF (1.8 g/kg) group, MGF (1.8 g/kg) group and oseltamivir (22.53 mg/kg) group, with 12 mice in each group. After continuous administration for 7 d, changes in body weight, anal temperature, survival rate, organ indexes, lung tissue pathology, levels of secretory immunoglobulin A (SIgA) in tracheal and bronchoalveolar lavage fluid, lung viral load, and serum inflammatory cytokine levels of mice in each group were detected. Results A total of 15 components including ephedrine, aconitine, sesamin ester and asarinin were detected in MXF, and 18 components including ephedrine, aconitine and liquiritin were detected in MGF. The content of ephedra alkaloids in MXF was higher than that in MGF. Compared with model group, all treatment groups were able to restore the body weight and anal temperature of mice, and the recovery effect was oseltamivir > MXF > MGF; There were no mouse deaths in oseltamivir and MXF groups, while one mouse died in MGF group; The lung index of oseltamivir group and MXF group were significantly decreased (P < 0.05, 0.01); The lung tissue lesions of mice in each treatment group were reduced, with the degree of reduction being oseltamivir > MXF > MGF; MXF had a higher clearance rate of lung viruses in mice; MGF significantly increased the level of SIgA in lung lavage fluid (P < 0.05); Oseltamivir, MXF and MGF could effectively reduce the total value of pro-inflammatory and anti-inflammatory factors, the ratio of pro-inflammatory and anti-inflammatory factors, and the proportion of pro-inflammatory factors, alleviate the body’s inflammatory response, and MGF had higher anti-inflammatory and immune enhancing effects than MXF; According to the box plot analysis of comprehensive therapeutic effects, MXF was superior to MGF. Conclusion Different adjuncts [Xixin (Asari Radix et Rhizoma/Gancao (Glycyrrhizae Radix et Rhizoma)] in MXF and MGF affect the contents of common components (ephedra alkaloids, aconitum alkaloids) in the formula; Both MXF and MGF could effectively treat kidney-yang deficiency and external infection syndrome and reduce the damage caused to the body by viral infection. Comparing the two, MXF has better comprehensive pharmacological effects, but MGF has better effects on inflammatory factors and immune regulation.

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国家自然科学基金资助项目（81873220）；2023年度济南市市校融合发展战略工程项目（JNSX2023054）；山东省技术创新引导计划（YDZX2023044）；国家中医药管理局高水平中医药重点学科建设项目（ZYYZDXK-2023119）；山东中医药大学科学研究基金项目（KY2024Z04）