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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
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