扶正化瘀方对代谢相关脂肪性肝炎的作用机制

肝脏 ›› 2025, Vol. 30 ›› Issue (11): 1534-1541.

扶正化瘀方对代谢相关脂肪性肝炎的作用机制

曾昊天, 李旭涛, 王四园, 阮天音, 陶艳艳, 冉云

102401 北京北京中医药大学(曾昊天);518172 深圳北京中医药大学深圳医院(曾昊天,冉云);201203 上海上海中医药大学附属曙光医院肝病研究所(李旭涛,王四园,阮天音,陶艳艳)

收稿日期:2025-02-07 出版日期:2025-11-30 发布日期:2026-02-09
通讯作者: 冉云,Email:35540785@qq.com

Exploring the mechanism of fuzheng huayu formula in preventing and treating metabolic dysfunction-associated steatohepatitis based on network pharmacology

ZENG Hao-tian^1,2, LI Xu-tao³, WANG Si-yuan³, RUAN Tian-yin³, TAO Yan-yan³, RAN Yun²

1. Beijing University of Chinese Medicine, Beijing 102401, China;
2. Beijing University of Chinese Medicine, Shenzhen Hospital(Longgang), Shenzhen 518172, China;
3. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received:2025-02-07 Online:2025-11-30 Published:2026-02-09
Contact: RAN Yun,Email:35540785@qq.com

摘要/Abstract

摘要： 目的探讨扶正化瘀方治疗代谢相关脂肪性肝炎的作用机制。方法以中药系统药理学数据库与分析平台(TCMSP)作为数据来源,筛选扶正化瘀方的主要活性成分及其对应的作用靶点,整合GeneCards数据库和OMIM数据库中的疾病相关数据,获取代谢相关脂肪性肝炎的潜在治疗靶点,取二者交集靶点进行蛋白相互作用(PPI)分析并获得核心蛋白信息,进行KEGG 富集分析以获取关键信号通路信息。选择SPF级小鼠40只,随机分为模型对照组、奥贝胆酸组、扶正化瘀组、正常对照组,每组10只。正常对照组喂养普通饲料,其他3组小鼠给予蛋氨酸胆碱缺乏(MCD)饲料,共8周。各药物组从第3周开始给药,共给药6周。末次给药12 h后,检测血清肝功能、肝组织TC、TG及羟脯氨酸含量;苏木素-伊红(HE)、天狼猩红及油红O染色观察肝组织病理变化,酶联免疫吸附试验检测肝组织IL-6、IL-1β和TNF-α表达,qRT-PCR和蛋白免疫印迹验证网络药理学富集信号分子。结果获得药物靶标与疾病病理靶点136个。PPI 网络和KEGG 富集分析显示,PI3K-Akt信号转导通路在靶点网络中显著富集(P<0.05),提示该通路可能作为扶正化瘀方干预代谢相关脂肪性肝炎的核心调控途径。相较于对照组,模型组小鼠血清AST、ALT及肝脏TC、TG表达水平升高,分别为(79.95±28.69)U/L、(147.60±27.11)U/L、(0.25±0.04)mmol/L、(0.51±0.09)mmol/L。扶正化瘀组小鼠血清的AST、ALT及肝脏TC、TG分别为(29.67±11.10)U/L、(62.41±20.13)U/L、(0.14±0.01)mmol/L、(0.20±0.06)mmol/L,较模型组降低,差异均有统计学意义(P<0.05)。扶正化瘀方可减轻小鼠肝组织IL-6、IL-1β和TNF-α,纤维化和脂肪蓄积,显著下调AKT1、NF-κB、HSP90、CASP9、BCL2、TP53 基因的表达,降低AKT、p-AKT、NF-κB、p-NF-κB、TP53蛋白表达水平。结论扶正化瘀方对代谢相关脂肪性肝炎小鼠具有一定的治疗作用,其作用机制可能与调节PI3K-Akt 信号通路有关。

关键词: 扶正化瘀方, 代谢相关脂肪性肝炎, 网络药理学, 作用机制

Abstract: Objective To investigate the mechanism of Fuzheng Huayu Formula (FZHY) in treating metabolic dysfunction-associated steatohepatitis (MASH). Methods The study utilized TCMSP to systematically analyze FZHY′s active ingredients and target proteins, while the potential MASH treatment targets were acquired by integrating data from GeneCards and OMIM resources.Intersecting targets were analyzed via protein-protein interaction (PPI) networks to identify core proteins, followed by KEGG enrichment analysis to determine key signaling pathways. A methionine-choline-deficient (MCD) diet-induced MASH mouse model was established. Mice were randomly divided into a model control group, an obeticholic acid group (10 mg/kg/day), a FZHY group (20.57 g crude drug/kg/day), and a normal control group (n=10/group). The MCD diet was administered to model and treatment groups for 8 weeks, while the normal control group received standard chow diet. Drug interventions began at week 3 and lasted for 6 weeks. Serum and liver tissues were collected 12 hours after the final dose. Serum liver function markers, hepatic total cholesterol (TC), triglycerides (TG), and hydroxyproline levels were measured using biochemical kits. Histopathological changes were assessed via hematoxylin-eosin (HE), Sirius red, and Oil Red O staining. Hepatic IL-6, IL-1β, and TNF-α levels were quantified by ELISA. Key network pharmacology-predicted signaling molecules were validated via qRT-PCR and Western blotting. Results The analysis yielded 136 shared targets between the drug′s action targets and disease pathogenesis targets. Both PPI network and KEGG pathway enrichment analyses demonstrated significant enrichment of the PI3K-Akt signaling transduction pathway (P<0.05), indicating its potential role as a pivotal regulatory pathway for FZHY′s therapeutic effects on MASH.The experimental results demonstrated that, compared with the control group, the model group exhibited elevated serum AST、ALT 、hepatic TC and TG levels, (79.95 ± 28.69) IU/L、(147.60 ± 27.11) IU/L and (0.25 ± 0.04) mmol/L、 (0.51 ± 0.09) mmol/L,FZHY treatment group showed significantly reduced serum AST、ALT、hepatic TC and TG levels, (29.67 ± 11.10) IU/L、(62.41 ± 20.13) IU/L and (0.14 ± 0.01) mmol/L、 (0.20 ± 0.06) mmol/L(P<0.05).Additionally, FZHY treatment alleviated hepatic IL-6, IL-1β, TNF-α levels, liver fibrosis, and liver lipid accumulation. It decreased mRNA expression of AKT1, NF-κB, HSP90, CASP9, BCL2, and TP53, and decreased protein levels of AKT, phosphorylated AKT (p-AKT), NF-κB, phosphorylated NF-κB (p-NF-κB), and TP53. Conclusion FZHY exerts therapeutic effects on MASH in mice, potentially through modulation of the PI3K-Akt signaling pathway.

Key words: Fuzheng Huayu Formula, Metabolic dysfunction-associated steatohepatitis, Network pharmacology, Mechanism

曾昊天, 李旭涛, 王四园, 阮天音, 陶艳艳, 冉云. 扶正化瘀方对代谢相关脂肪性肝炎的作用机制[J]. 肝脏, 2025, 30(11): 1534-1541.

ZENG Hao-tian, LI Xu-tao, WANG Si-yuan, RUAN Tian-yin, TAO Yan-yan, RAN Yun. Exploring the mechanism of fuzheng huayu formula in preventing and treating metabolic dysfunction-associated steatohepatitis based on network pharmacology[J]. Chinese Hepatolgy, 2025, 30(11): 1534-1541.

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