基于网络药理学及病理学分析小建中汤化裁方对大鼠甲状腺结节的作用机制

Mechanistic Study of a Modified Xiaojianzhong Decoction on Thyroid Nodules in Rats Based on Network Pharmacology and Histopathological Analysis

摘要: 目的：基于网络药理学及病理学分析小建中汤化裁方治疗甲状腺结节的作用。方法：将大鼠随机分为空白组、模型组及小建中汤高、中、低剂量组，共五组；采用丙硫氧嘧啶造模，并分别给予相应药物干预。给药12周后伊红–苏木素染色观察甲状腺组织形态学变化。利用TCMSP、PubChem、SwissTargetPrediction数据库筛选复方有效成分与靶点，构建药物成分–靶点–通路网络图，并进行KEGG和GO富集分析。结果：动物实验显示，与模型组相比，小建中汤干预后大鼠甲状腺组织学形态出现改善，滤泡结构趋于规则，滤泡腔内胶质含量增加，间质血管扩张程度减轻，其中高剂量组改善最为显著，提示小建中汤可能对模型所致甲状腺组织损伤具有剂量依赖性的保护作用。网络药理学获得小建中汤活性成分125个，靶点903个，交集靶点318个，核心靶点为EGFR、AKT1、BCL2、NFKB1等，主要涉及腺癌相关疾病的信号通路、PI3K-Akt信号通路、表皮生长因子受体酪氨酸激酶抑制剂耐药性等信号通路。结论：小建中汤化裁方可能通过调节EGFR介导的PI3K-Akt信号转导，抑制AKT磷酸化水平，下调BCL2表达并调控NF-κB活性，从而改善甲状腺滤泡上皮异常增殖及炎症微环境。

Abstract: Objective: To investigate the effects and underlying mechanisms of a modified Xiaojianzhong Decoction (XJZD) on thyroid nodules in rats based on network pharmacology and histopathological analysis. Methods: Rats were randomly divided into five groups: a normal control group, a model group, and three treatment groups receiving high-, medium-, and low-dose modified XJZD. A thyroid nodule model was established using propylthiouracil, followed by corresponding drug interventions. After 12 weeks of treatment, thyroid tissues were collected for hematoxylin-eosin (H&E) staining to observe histopathological changes. Active components and potential targets of XJZD were screened using the TCMSP, PubChem, and SwissTargetPrediction databases. A compound-target-pathway network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results: Compared with the model group, XJZD treatment improved thyroid histopathological alterations in rats, characterized by a more regular follicular architecture, increased colloid content, and reduced interstitial vascular dilation. The high-dose group exhibited the most pronounced improvement, suggesting a dose-dependent protective effect. Network pharmacology identified 125 active compounds and 903 potential targets of XJZD, with 318 overlapping targets related to thyroid nodules. Core targets included EGFR, AKT1, BCL2, and NFKB1. Enrichment analysis indicated that the therapeutic effects were mainly associated with adenocarcinoma-related signaling pathways, the PI3K-Akt signaling pathway, and pathways related to epidermal growth factor receptor tyrosine kinase inhibitor resistance. Conclusion: Modified Xiaojianzhong Decoction may exert therapeutic effects on thyroid nodules by modulating EGFR-mediated PI3K-Akt signaling, inhibiting AKT phosphorylation, downregulating BCL2 expression, and regulating NF-κB activity, thereby ameliorating abnormal proliferation of thyroid follicular epithelial cells and the inflammatory microenvironment.