目的 探究黄芩茎叶总黄酮（SSTF）治疗溃疡性结肠炎（UC）合并贫血的药效及作用机制。方法 通过文献查阅和Swiss Target Prediction数据库获取SSTF中黄酮成分及其作用靶点；通过GeneCards、OMIM和TTD数据库收集UC合并贫血疾病靶点；使用Venny 2.1绘图软件获取药物和疾病交集靶点；将交集靶点导入STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络；采用Metascape数据平台进行基因本体（GO）功能和京都基因和基因组百科全书（KEGG）通路富集分析；再采用AutoDock 1.5.7软件对主要活性成分和关键靶点进行分子对接。利用噁唑酮建立UC小鼠模型，模型成功小鼠随机分为模型组、溶媒（0.5%羧甲基纤维素钠）组、柳氮磺吡啶肠溶片（SASP，阳性药，450 mg·kg⁻¹）组和SSTF低、中、高剂量（26、52、104 mg·kg⁻¹）组，每组15只。另设15只小鼠作为对照组，不造模。各治疗组从第9天开始ig相应药物，对照组与模型组给予0.9%的氯化钠溶液，每天1次，连续7 d。从第8天开始每天称小鼠体质量，进行疾病活动指数（DAI）评分；给药结束后取材，测量结肠长度，对脾脏组织称质量，并计算脾脏指数；苏木素-伊红（HE）染色进行结肠组织病理学检查，酶联免疫吸附试验（ELISA）试剂盒法检测血清肿瘤坏死因子α（TNF-α）、白细胞介素10（IL-10）、促红细胞生成素（EPO）、血红蛋白（HGB）、铁（SI）、铁蛋白（SF）、铁调素（Hepcidin）和可溶性转铁蛋白受体（sTfR）水平，实时荧光定量PCR（qRT-PCR）法检测脾组织促红细胞生成素受体（EPOR）、赤铁酮（ERFE）、膜铁转运蛋白（FPN/SLC40A1）和肝组织铁调素（Hepcidin）、FPN mRNA表达。结果 网络药理学结果表明，SSTF中27个黄酮成分可作用于EPO、EPOR等25个交集靶点，调控JAK/STAT等信号通路。分子对接结果表明主要活性成分黄芩苷、汉黄芩苷、木犀草素、野黄芩苷、野黄芩素、芹菜素与关键靶点间结合稳定。体内实验结果表明，与模型组比较，SSTF组小鼠体质量显著升高、DAI评分显著降低、脾脏指数显著降低、结肠长度显著增加（P＜0.05、0.01）；结肠组织病理损伤明显改善；血清中Hepcidin、sTfR、TNF-α水平显著降低（P＜0.05、0.01），血清SF、SI、HGB、EPO、IL-10水平显著升高（P＜0.05、0.01）；小鼠脾组织中EPOR、ERFE、FPN mRNA表达水平和肝组织中FPN mRNA表达水平显著升高（P＜0.05、0.01），肝组织中Hepcidin mRNA表达水平显著降低（P＜0.05）。结论 SSTF可通过调节EPOR/ERFE/FPN信号轴治疗UC合并贫血。

Objective To explore the efficacy and mechanism of action of Scutellaria Baicalensis stem-leaf total flavonoids (SSTF) in the treatment of ulcerative colitis (UC) complicated with anemia. Methods The flavonoid components and their target sites in the stems and leaves of Scutellaria baicalensis were obtained through literature review and the Swiss Target Prediction database. The target sites of ulcerative colitis (UC) combined with anemia were collected from the GeneCards, OMIM and TTD databases. The Venny 2.1 drawing software was used to obtain the intersection target sites of drugs and diseases. The intersection target sites were imported into the STRING database to construct a protein-protein interaction (PPI) network. The Metascape data platform was used for gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The AutoDock 1.5.7 software was used for molecular docking of the main active components and key target sites. The UC mouse model was established by using oxazolone. The successfully modeled mice were randomly divided into the model group, the solvent (0.5% carboxymethyl cellulose sodium) group, the sulfasalazine enteric-coated tablet (SASP, positive drug, 450 mg·kg⁻¹) group and the SSTF low, medium and high dose (26, 52, 104 mg·kg⁻¹) groups, with 15 mice in each group. Another 15 mice were set as the control group without modeling. The treatment groups were given the corresponding drugs by intragastric administration from the 9th day, while the control group and the model group were given 0.9% sodium chloride solution once a day for seven consecutive days. The body weight of the mice was measured every day from the 8th day, and the disease activity index (DAI) score was evaluated. After drug administration, the colon length was measured, the spleen tissue was weighed and the spleen index was calculated. The colon tissue was stained with hematoxylin-eosin (HE) for histopathological examination. The levels of serum tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), erythropoietin (EPO), iron (SI), ferritin (SF), hepcidin and soluble transferrin receptor (sTfR) were detected by enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expressions of erythropoietin receptor (EPOR), erythroferrone (ERFE), ferroportin (FPN/SLC40A1) in spleen tissue and hepcidin, FPN and Hepcidin in liver tissue were detected by real-time fluorescence quantitative PCR (qRT-PCR). Results The results of network pharmacology indicated that 27 flavonoid components in SSTF could act on 25 intersection targets such as EPO and EPOR, and regulate signaling pathways such as JAK/STAT. The results of molecular docking showed that the main active components, baicalin, wogonin, luteolin, scutellarein, and apigenin, had stable binding with key targets. The in vivo experiments demonstrated that compared with the model group, the body weight of mice in the SSTF group significantly increased, the DAI score significantly decreased, the spleen index significantly decreased, and the colon length significantly increased (P < 0.05, 0.01); the pathological damage of colon tissue was significantly improved; the levels of Hepcidin, sTfR, and TNF-α in serum significantly decreased (P < 0.05, 0.01), while the levels of SF, SI, HGB, EPO, and IL-10 in serum significantly increased (P < 0.05, 0.01); the mRNA expression levels of EPOR, ERFE, and FPN in spleen tissue and FPN in liver tissue significantly increased (P < 0.05, 0.01), and the mRNA expression level of Hepcidin in liver tissue significantly decreased (P < 0.05). Conclusion SSTF can treat UC combined with anemia by regulating the EPOR/ERFE/FPN signaling axis.

R285.5

泰州市“凤城英才计划”青年科技人才托举工程（TZ-018）