目的 探索玄参水提物（SNAE）对肾阴虚水肿大鼠的治疗作用及对体内物质与能量代谢的影响。方法 将48只雄性SD大鼠随机分为对照组、阴虚组、阴虚恢复组、阴虚水肿模型组、SNAE（2.7 g·kg^-1）组和呋塞米（阳性药，3.6 mg·kg^-1）组，每组8只。除对照组ig 0.9%氯化钠溶液外，其余各组均ig给予甲状腺素和利血平注射液混合物，连续10 d，制备大鼠肾阴虚模型；于第11天ip给予阴虚水肿模型组、SNAE组和呋塞米组氨基核苷嘌呤霉素（PAN）溶液，制备肾源性水肿模型，阴虚恢复组和对照组ip给予0.9%氯化钠溶液；于12 d起ig给药，每天1次。于取材的前1天禁食、不禁水12 h，阴虚组于第11天、其他组于第18天取材。取肾组织进行苏木素-伊红（HE）染色后光镜下观察、透射电镜下肾脏超微病理学观察；全自动生化仪检测血清肌酐（Scr）、尿素氮（BUN）、总蛋白（TP）、血浆白蛋白（ALB）以及尿液中尿蛋白（UP）水平，试剂盒法检测血清睾酮（T）、雌二醇（E₂）、三碘甲状腺原氨酸（T₃）、甲状腺素（T₄）水平以及环磷酸腺苷（cAMP）/环磷酸鸟苷（cGMP）；应用UPLC-Q-TOF-MS技术对各组大鼠尿液进行分析，通过多变量统计分析筛选潜在生物标志物，结合人类代谢组学数据库（HMDB）和Metlin在线数据库鉴定重要生物标志物，并将鉴定到的生物标志物导入京都基因与基因组百科全书数据库（KEGG）推测其可能的代谢通路。结果 病理学结果显示，与对照组、阴虚组、阴虚恢复组相比，阴虚水肿模型组肾脏病理损伤较明显；与阴虚水肿组比较，SNAE、呋塞米对模型大鼠病理损伤程度有明显改善作用；在药效学指标上，与阴虚水肿模型组比较，SNAE能显著下调Scr、BUN、T₄水平（P<0.05），显著上调T、E₂、cAMP/cGMP、TP、ALB水平（P<0.05、0.01）；代谢组学结果显示，SNAE可改善各阴虚组大鼠代谢轨迹的偏离。通过对大鼠尿液代谢产物变化的预测，得到符合要求的生物标志物共14个，包括柠檬酸、磷酸烯醇式丙酮酸、6-磷酸葡萄糖酸、尿酸、庚二酸、2-异丙基苹果酸等；涉及15条相关代谢通路，关键代谢途径主要富集于三羧酸（TCA）循环。结论 SNAE通过调节能量代谢相关通路发挥“滋阴、利水”等功效，从而对肾阴虚水肿发挥治疗作用。

Objective Exploring the therapeutic effect of Scrophularia ningpoensis aqueous extract (SNAE) on edema caused by kidney yin deficiency in rats and its impact on substance and energy metabolism in the body. Methods Forty-eight male SD rats were randomly divided into control group, Yin deficiency group, Yin deficiency recovery group, Yin deficiency edema group, SNAE (2.7 g·kg^-1) group and furosemide (positive, 3.6 mg·kg^-1) group, with eight rats in each group. Except control group, which was given 0.9% sodium chloride solution by ig, the other groups were ig given the mixture of thyroxine and rexepin injection intragastric for 10 consecutive days to replicate the model of kidney-yin deficiency in rats. On the 11th day, the edema group, furosemide group and SNAE group were ip given puromycin aminonucleoside (PAN) solution to replicate the model of nephrogenic edema, and the Yin deficiency recovery group and the control group were given 0.9% sodium chloride solution via ip. Administer ig once a day starting from 12 days. On the day before sampling, fasting and uncontrollable hydration were performed for 12 hours. Administer ig once a day starting from 12 days. The Yin deficiency group was sampled on the 11th day, while the other groups were sampled on the 18th day. Taked kidney tissue for hematoxylin eosin (HE) staining and observed under light microscopy and transmission electron microscopy for renal ultrastructural pathology. The automatic biochemical analyzer detected serum creatinine (Scr), urea nitrogen (BUN), total protein (TP), plasma albumin (ALB), and urine protein (UP) levels. The kit method detected serum testosterone (T), estradiol (E₂), triiodothyronine (T₃), thyroxine (T₄) levels, as well as cyclic adenosine monophosphate (cAMP)/ cyclic guanosine monophosphate (cGMP) levels. Applied UPLC-Q-TOF-MS technology to analyze the urine of rats in each group, screen potential biomarkers through multivariate statistical analysis, and combined with the human metabolomics database (HMDB) to search and literature identification of important biomarkers. Imported the identified biomarkers into the Kyoto Encyclopedia of Genes and Genomes database (KEGG) to speculate their possible metabolic pathways. Results The pathological results showed that compared with the control group, Yin deficiency group, and Yin deficiency recovery group, the kidney pathological damage in the Yin deficiency edema model group was more significant. Compared with the Yin deficiency edema group, SNAE and furosemide had a significant improvement effect on the degree of pathological damage in model rats. In terms of pharmacodynamic indicators, compared with the Yin deficiency edema model group, SNAE significantly downregulated the levels of Scr, BUN, and T₄ (P< 0.05), and significantly upregulated the levels of T, E₂, cAMP/cGMP, TP, and ALB (P< 0.05, 0.01). Metabolomics results showed that SNAE can improve the deviation of metabolic trajectories in rats of various yin deficiency groups. By predicting changes in metabolic products in rat urine, a total of 14 biomarkers were obtained that meet the requirements, including citric acid, phosphoenolpyruvate, 6-phosphogluconic acid, uric acid, succinic acid, 2-isopropylmalic acid, etc. It involves 15 related metabolic pathways, with key metabolic pathways mainly enriched in the tricarboxylic acid (TCA) cycle. Conclusion SNAE exerts therapeutic effects on kidney yin deficiency and edema by regulating energy metabolism related pathways, such as nourishing yin and promoting diuresis.

国家重点基础研究发展计划（973计划）资助项目（2013CB531804）；黑龙江中医药大学优秀创新人才支持计划资助（15041180088）