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基于“肠-肝轴”探讨胃苓汤对代谢相关脂肪性肝病的改善作用
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| 篇名： | 基于“肠-肝轴”探讨胃苓汤对代谢相关脂肪性肝病的改善作用 |
| TITLE： | Ameliorative effect of Weiling decoction on metabolic associated fatty liver disease based on the gut-liver axis |
| 摘要： | 目的 基于“肠-肝轴”理论，探讨胃苓汤对代谢相关脂肪性肝病（MAFLD）的改善作用。方法将雄性C57BL/6J小鼠分为空白组（9只）和造模组（47只），其中造模组小鼠以高脂饲料喂养12周以构建MAFLD模型。将45只造模小鼠随机分为模型组、阳性对照组[二甲双胍，0.2g/（kg·d）]和胃苓汤低、中、高剂量组[6.17、12.34、24.68g/（kg·d），以生药量计]，每组9只。各组小鼠每天灌胃相应药液或生理盐水1次，连续4周。末次给药后，比较各组小鼠体重、肝脏质量及肝脏指数，检测其肝功能（丙氨酸转氨酶、天冬氨酸转氨酶）、血脂（总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇）、炎症[肿瘤坏死因子α、白细胞介素6（IL-6）、IL-1β]、氧化应激（丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶）及肠道屏障[脂多糖（LPS）、二胺氧化酶、D-乳酸]相关指标水平，观察其肝组织病理改变，检测其空肠组织中紧密连接蛋白[闭锁小带1（ZO-1）、闭合蛋白（occludin）]和肝组织中脂质代谢[固醇调节元件结合蛋白1（SREBP-1）、脂肪酸合酶（FASN）、过氧化物酶体增殖物激活受体α（PPARα）]、炎症通路[Toll样受体4（TLR4）、髓系分化初级反应蛋白88（MyD88）、核因子κBp65（NF-κBp65）]相关蛋白的表达情况，并分析其肠道菌群变化情况。结果与模型组相比，胃苓汤各剂量组小鼠肝组织脂肪变性和炎症损伤均明显减轻，体重（实验第16周）、肝脏质量、肝脏指数和肝功能、血脂、炎症、氧化应激、肠道屏障相关指标均普遍改善（P＜0.05）；肝组织中SREBP-1、FASN、TLR4、MyD88蛋白的表达和NF-κBp65蛋白的磷酸化水平均普遍降低或下调（P＜0.05），空肠组织中ZO-1、occludin蛋白和肝组织中PPARα蛋白的表达均普遍升高或上调（P＜0.05）。与模型组相比，胃苓汤高剂量组小鼠肠道菌群的Observedspecies、Chao1、Ace指数均显著回升（P＜0.05），且其疣微菌门、阿克曼菌属等菌群的相对丰度均显著升高，放线菌门和另枝菌属、粪杆菌属等菌群的相对丰度均显著降低（P＜0.05）。结论胃苓汤可改善MAFLD，其作用可能与调节肠道菌群、修复肠道机械屏障、减少LPS易位，进而抑制TLR4/MyD88/NF-κB炎症通路、减轻氧化应激，并调节SREBP-1/FASN与PPARα介导的脂质代谢有关。 |
| ABSTRACT： | OBJECTIVE To investigate the ameliorative effect of Weiling decoction on metabolic associated fatty liver disease （MAFLD） based on the gut-liver axis theory.METHODS Male C57BL/6J mice were divided into a blank group （ n ＝9） and a modeling group （ n ＝47）. The modeling group was fed a high-fat diet for 12 weeks to establish the MAFLD model. Forty-five modeled mice were randomly divided into a model group， a positive control group [metformin， 0.2 g/（kg·d）]， and Weiling decoction low-， medium-， and high-dose groups [6.17， 12.34， 24.68 g/（kg·d）， calculated as crude drug]， with 9 mice in each group. Mice in each group received intragastric administration of the corresponding drug solution or normal saline once daily for 4 consecutive weeks. After the last administration， the body weight， liver weight， and liver index were compared among groups； the levels of liver function indicators （alanine transaminase， aspartate transaminase）， lipid indicators （total cholesterol， triglycerides， low-density lipoprotein cholesterol， high-density lipoprotein cholesterol）， inflammatory indicators [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β]， oxidative stress indicators （malondialdehyde， superoxide dismutase， glutathione peroxidase）， and intestinal barrier indicators [lipopolysaccharide （LPS）， diamine oxidase， D-lactic acid] were measured； hepatic pathological changes were observed； the expressions of tight junction proteins [zonula occludens-1 （ZO-1）， occludin] in jejunal tissue and proteins related to lipid metabolism [sterol regulatory element-binding protein-1 （SREBP-1）， fatty acid synthase （FASN）， peroxisome proliferator-activated receptor α （PPARα）] and inflammatory pathways [Toll-like receptor 4 （TLR4）， myeloid differentiation primary response protein 88 （MyD88）， nuclear factor-κB p65 （NF-κB p65）] in liver tissue were detected； and changes in gut microbiota were analyzed.RESULTS Compared with the model group， hepatic steatosis and inflammatory injury were significantly alleviated in all Weiling decoction dose groups； body weight （at week 16）， liver weight， liver index， and the levels of liver function indicators， lipid indicators， inflammation indicators， oxidative stress indicators， and intestinal barrier indicators were all generally improved （ P ＜0.05）. The expressions of SREBP-1， FASN， TLR4， and MyD88 and the phosphorylation level of NF-κB p65 in liver tissue were generally decreased or downregulated （ P ＜0.05）， while the expressions of ZO-1 and occludin in jejunal tissue and PPARα in liver tissue were generally increased or upregulated （ P ＜0.05）. Compared with the model group， the Observed species， Chao1， and Ace indices of gut microbiota in the Weiling decoction high-dose group were significantly increased （ P ＜0.05）， and the relative abundances of Verrucomicrobiota， Akkermansia ， etc. were significantly increased， while those of Actinomycetota， Alistipes ， Faecalibaculum ， etc. were significantly decreased （ P ＜0.05）.CONCLUSIONS Weiling decoction can ameliorate MAFLD， and its effect may be associated with regulating gut microbiota， repairing the intestinal mechanical barrier， reducing LPS translocation， thereby inhibiting the TLR4/MyD88/NF-κB inflammatory pathway， alleviating oxidative stress， and regulating SREBP-1/FASN and PPARα-mediated lipid metabolism. |
| 期刊： | 2026年第37卷第19期 |
| 作者： | 崔蓓蕾；宋艺佳；管雅捷；张琪振；吴文静；徐俊姣；刘鸣昊 |
| AUTHORS： | CUI Beilei，SONG Yijia，GUAN Yajie，ZHANG Qizhen，WU Wenjing，XU Junjiao，LIU Minghao |
| 关键字： | 胃苓汤;代谢相关脂肪性肝病;肠-肝轴;肠道菌群;肠道屏障;脂质代谢;TLR4/MyD88/NF-κB信号通路;SREBP-1/FASN信号轴;PPARα信号通路 |
| KEYWORDS： | Weiling decoction;metabolic associated fatty liver disease;gut-liver axis;gut microbiota;Intestinal barrier;Lipid metabolism;TLR4/MyD88/NF-κB signaling pathway;SREBP-1/FASN signaling axis;PPARα signaling pathway |
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