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基于肠道菌群和代谢组学研究金刚藤胶囊治疗非酒精性脂肪肝
的作用及机制
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程世源 ,熊 悦 ,张丹丹 ,李 晶 ,孙志滢 ,田家瑛 ,沈 丽 ,沈 月 ,刘 丹 ,魏 琼 ,叶晓川 (1.湖
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北中医药大学药学院中药资源与中药化学湖北省重点实验室,武汉 430065;2.湖北科技学院医学部药学院糖
尿病心脑血管病变省级重点实验室,湖北 咸宁 437099;3.湖北时珍实验室,武汉 430065)
中图分类号 R965;R285.5;R575 文献标志码 A 文章编号 1001-0408(2025)11-1340-08
DOI 10.6039/j.issn.1001-0408.2025.11.09
摘 要 目的 探究金刚藤胶囊治疗非酒精性脂肪性肝病(NAFLD)的作用及机制。方法 将32只SD大鼠随机分为正常组和造模
组,造模组以高脂饲料喂养构建NAFLD大鼠模型。将造模成功的大鼠随机分为模型组、阿托伐他汀组[阳性对照,2 mg/(kg·d)]和
金刚藤胶囊低、高剂量组[0.63、2.52 mg/(kg·d)],每组6只。采用苏木素-伊红染色、油红O染色观察肝脏病理变化;酶联免疫吸附
试验测定大鼠血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶
(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6、IL-18水平。应用16S rDNA 测序和非靶
向代谢组学技术分析金刚藤胶囊对NAFLD大鼠肠道菌群和代谢的调控作用;基于代谢组学结果,采用Western blot法对NAFLD
大鼠肝脏中核因子 κB(NF-κB)/NOD 样受体家族蛋白 3(NLRP3)信号通路相关蛋白进行检测。结果 金刚藤胶囊可以显著降低
NAFLD大鼠TG、TC、LDL-C、AST、ALT、TNF-α、IL-1β、IL-6、IL-18水平,提高HDL-C水平(P<0.05或P<0.01),减轻肝脏细胞脂
肪变性及炎性浸润;能调节NAFLD大鼠的肠道菌群紊乱,显著增加Oscillospira、Romboutsia两种菌属的相对丰度,显著降低Blau‐
tia 的相对丰度(P<0.05);主要通过影响次级胆汁酸生物合成、脂肪酸降解、O-抗原核苷酸糖生物合成等途径调节代谢紊乱。
Western blot法检测结果显示,该药可以显著降低NF-κB p65、NF-κB抑制因子α的磷酸化水平和NLRP3、胱天蛋白酶1、抗体分泌
细胞蛋白表达水平(P<0.05或P<0.01)。结论 金刚藤胶囊可改善NAFLD大鼠的炎症反应、脂质积累和肝脏损伤,调节肠道微生
态及代谢紊乱,通过抑制NF-κB/NLRP3信号通路发挥治疗NAFLD的作用。
关键词 金刚藤胶囊;非酒精性脂肪肝;肠道菌群;代谢组学;NF-κB/NLRP3信号通路
Effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease based on
gut microbiota and metabolomics
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CHENG Shiyuan ,XIONG Yue ,ZHANG Dandan ,LI Jing ,SUN Zhiying ,TIAN Jiaying ,SHEN Li ,SHEN
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Yue ,LIU Dan ,WEI Qiong ,YE Xiaochuan (1. Hubei Provincial Key Laboratory of Chinese Medicinal
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Material Resources and Chinese Medicine Chemistry, School of Pharmacy, Hubei University of Chinese
Medicine, Wuhan 430065, China;2. Provincial Key Laboratory for Cardio-Cerebrovascular Diseases in Diabetes
Mellitus, School of Pharmacy, Faculty of Medicine, Hubei University of Science and Technology, Hubei
Xianning 437099, China;3. Hubei Shizhen Laboratory, Wuhan 430065, China)
ABSTRACT OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic
fatty liver disease (NAFLD). METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The
modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided
into model group, atorvastatin group[positive control, 2 mg/(kg·d)], and Jingangteng capsules low- and high-dose groups [0.63
and 2.52 mg/(kg·d)], with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining
and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides (TG),
total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine
transaminase (ALT), aspartate transaminase (AST), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18. 16S
rDNA amplicon sequencing and metabolomics techniques were
Δ 基金项目 湖北省自然科学基金项目(No.2023AFB513);湖北省
applied to explore the effects of Jingangteng capsules on gut
科技重大专项(No.2020ACA007)
*第一作者 硕士研究生。研究方向:中药物质基础及作用机制。 microbiota and metabolisms in NAFLD rats. Based on the
E-mail:591146765@qq.com metabolomics results, Western blot analysis was performed to
# 通信作者 教授,博士生导师。研究方向:中药药效物质及作用 detect proteins related to the nuclear factor kappa-B (NF-κB)/
机制。E-mail:yxxcc1965@163.com NOD-like receptor family protein 3 (NLRP3) signaling
· 1340 · China Pharmacy 2025 Vol. 36 No. 11 中国药房 2025年第36卷第11期