目的 探讨当归六黄汤的抗阴虚甲亢作用，阐释传统汤剂合煎和单煎的差异。方法 运用网络药理学方法，筛选当归六黄汤的主要活性成分和治疗阴虚甲亢疾病的相关靶点，并对交集靶点进行蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络分析、基因本体（gene ontology，GO）功能和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析，构建药材-成分-靶点-通路网络；进一步进行实验验证，构建阴虚甲亢大鼠模型，评价当归六黄汤合煎和单煎对阴虚甲亢大鼠体质量、粪便含水率及相关血清学指标的影响；利用16S rDNA测序技术，揭示合煎和单煎对大鼠肠道微生物群落多样性的影响。结果 筛选获得当归六黄汤方中102个活性成分，检索出与阴虚甲亢有关靶点116个。富集分析获得871条GO条目和158条KEGG相关条目（P＜0.05），其中生物过程（biological process，BP）675条、细胞组分（cellular component，CC）77条、分子功能（molecular function，MF）119条，与当归六黄汤相关度较高的通路主要包括炎症、感染、肠病、癌症等通路。抗阴虚甲亢药效作用结果表明，与模型组比较，合煎高剂量组大鼠的体质量净增值和粪便含水率均显著增加（P＜0.01），三碘甲状腺原氨酸（three iodine thyroid，T3）、甲状腺素（tetraiodothyronine，T4）等激素水平显著降低（P＜0.01），且作用接近阳性药甲巯咪唑组。大鼠肠道菌群多样性结果显示，合煎高剂量组大鼠肠道微生物的丰富度和多样性接近对照组，Lachnospiraceae_NK4A136_group在模型组大鼠肠道显著富集，合煎给药后阿克曼氏菌属Akkermansia相对丰度明显增加，而单煎给药后普雷沃氏菌属Prevotella相对丰度明显增加。结论 当归六黄汤合煎抗阴虚甲亢药效作用更好；阴虚甲亢等内分泌紊乱性疾病极有可能致肠道微生物群紊乱，当归六黄汤合煎可能通过调节肠道微生物群的方式治疗阴虚甲亢。

Objective To investigate the anti-yin-deficiency-hyperthyroidism effect of Danggui Liuhuang Decoction (当归六黄汤), and explain the difference between all-herb decoction and single-herb decoction. Methods The network pharmacology method was used to screen the main active components of Danggui Liuhuang Decoction and related targets for the treatment of yin-deficiency-hyperthyroidism. The protein-protein interaction (PPI) network analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the intersection targets to construct the herb-component-target-pathway network. Further experimental verification was performed, yin-deficiency-hyperthyroidism rat model was constructed, effect of all-herb decoction and single-herb decoction of Danggui Liuhuang Decoction on body weight, fecal water content and related serological indicators of yin-deficiency-hyperthyroidism rats were evaluated. The effects of all-herb decoction and single-herb decoction on the diversity of intestinal microbial community in rats were revealed by 16S rDNA sequencing. Results A total of 94 active components in Danggui Liuhuang Decoction were screened and 116 targets related to yin-deficiency-hyperthyroidism were found. Enrichment analysis obtained 871 GO items and 158 KEGG related items (P < 0.05), including 675 biological processes (BP), 77 cellular components (CC), and 119 molecular functions (MF). The pathways with high correlation with Danggui Liuhuang Decoction mainly included inflammation, infection, intestinal disease, cancer and other pathways. The results of anti-yin-deficiency-hyperthyroidism efficacy showed that compared with model group, the net weight gain and fecal moisture content of rats in all-herb decoction high-dose group were significantly increased (P < 0.01), levels of triiodothyronine (T3) and thyroxine (T4) were significantly decreased (P < 0.01), and the effect was close to the positive drug methimazole group. The results of intestinal flora diversity in rats showed that the richness and diversity of intestinal microorganisms in all-herb decoction high-dose group were close to those in control group. Lachnospiraceae_NK4A136_group was significantly enriched in the intestinal tract of model rats. Akkermansia was significantly increased after administration of all-herb decoction, while Prevotella was significantly increased after administration of single-herb decoction. Conclusion The effect of Danggui Liuhuang Decoction for anti-yin-deficiency-hyperthyroidism is better. Endocrine disorders such as yin-deficiency-hyperthyroidism is likely to cause intestinal microflora disorders, Danggui Liuhuang Decoction may be through the regulation of intestinal microflora in the treatment of yin-deficiency-hyperthyroidism.

吉林省科技发展计划项目（20210204032YY）