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| 间歇性禁食联合苓桂术甘汤和益生元对非酒精性脂肪肝小鼠的作用研究* |
| The study investigates the effects of intermittent fasting combined with the decoction of Ling-gui-zhu-gan and prebiotics on mice with non-alcoholic fatty liver disease |
| 投稿时间：2024-06-13 修订日期：2024-06-14 |
| DOI： |
| 中文关键词: 非酒精性脂肪肝 肠道菌群 间歇性禁食 苓桂术甘汤 益生元 |
| 英文关键词: Non-alcoholic fatty liver disease gut microbiota intermittent fasting Ling-gui-zhu-gan decoction prebiotics |
| 基金项目:北京中医药大学高层次人才科研启动项目(90011451310015)。 |
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| 中文摘要: |
| 目的:探究间歇性禁食联合苓桂术甘汤和益生元对非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的治疗效果及内在机制。方法:通过12周高脂饮食(High-fat diet, HFD)喂养建立NAFLD小鼠模型,干预方式包括单纯间歇性禁食组(Intermittent Fasting, IF)、禁食联合低浓度苓桂术甘汤组(IFLGL)、禁食联合高浓度苓桂术甘汤组(IFLGH)、禁食联合益生元组(IFpre)、禁食联合益生元和高浓度苓桂术甘汤组(IFLGpre)。检测各组小鼠的体重、血清生化指标、肝脏组织学染色、肠道菌群变化和SREBP-1通路相关基因的表达情况。结果:与模型组相比,IF组、IFLGL组、IFLGH组、IFpre和IFLGpre组的小鼠体重,血生化指标丙氨酸转氨酶(Alanine transaminase, ALT)、天冬氨酸转氨酶(Aspartate transaminase, AST)、胆固醇(Cholesterol, CHO)、甘油三酯(Triglyceride, TG)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol, HDL-C)和低密度脂蛋白胆固醇(Low Density Lipoprotein, LDL-C)均显著降低(P＜0.01)；包括间歇性禁食在内的5种干预方式有效缓解了高脂饮食喂养诱发的肝脏脂质过量积累和脂肪变性,肝组织病理损伤得到改善；与对照组相比,模型组的菌群α多样性指标ACE、Chao1和Simpson指数显著降低(P＜0.05),在IF组、IFLGH组、IFpre组和IFLGpre组干预后显著升高(P＜0.01)。在目水平上,所有的干预方式均显著提高了组内乳酸菌(Lactobacillale)和双歧杆菌(Bifidobacteriale)等益生菌的含量；IFLGpre组与其他干预组相比,在体重、肝功能指标ALT和AST,血脂指标TG、CHO和HDL-C,肝脏组织学以及肠道菌群测序等多项结果中治疗效果更显著,且差异具有统计学意义。包括间歇性禁食在内的5种干预方式均显著下调了肝脏SREBP-1通路中的SREBP-1c和FAS基因的表达水平(P ＜ 0.01),缓解了肝脏的脂质过量积累。结论:间歇性禁食联合苓桂术甘汤和益生元可以通过调节肠道菌群和SREBP-1通路改善NAFLD,且联合干预模式的治疗效果更显著。 |
| 英文摘要: |
| Objective:The aim of this study was to investigate the therapeutic effects and underlying mechanisms of intermittent fasting combined with Ling-gui-zhu-gan decoction and prebiotics on non-alcoholic fatty liver disease (NAFLD). Methods:A mouse model of NAFLD was established by feeding with a high-fat diet (HFD) for 12 weeks, followed by different interventions including simple intermittent fasting (IF), intermittent fasting combined with low-dose Ling-gui-zhu-gan decoction (IFLGL), intermittent fasting combined with high-dose Ling-gui-zhu-gan decoction (IFLGH), intermittent fasting combined with prebiotics (IFpre), and intermittent fasting combined with prebiotics and high-dose Ling-gui-zhu-gan decoction (IFLGpre). Changes in body weight, blood biochemical parameters, liver histology, gut microbiota, and expression of Srebp-1 pathway-related genes were measured. Results:Compared with the model group, mice in the IF group, IFLGL group, IFLGH group, IFpre group, and IFLGpre group showed significant reductions in body weight and blood biochemical parameters including alanine transaminase (ALT), aspartate transaminase (AST), cholesterol (CHO), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) (P < 0.01). All five intervention methods including intermittent fasting effectively alleviated hepatic lipid accumulation and steatosis induced by HFD feeding, and improved liver tissue pathology. Compared with the control group, the model group showed significantly decreased alpha diversity indices of gut microbiota, including ACE, Chao1, and Simpson indices (P < 0.05), which were significantly increased after interventions in the IF group, IFLGH group, IFpre group, and IFLGpre group (P < 0.01). At the order level, all intervention methods significantly increased the levels of beneficial bacteria such as Lactobacillales and Bifidobacteriales. Compared to other intervention groups, the IFLGpre group showed the best treatment effects in terms of body weight, liver function indicators (ALT and AST), blood lipid indicators (TG, CHO, and HDL-C), liver histology, and gut microbiota sequencing, with these differences being statistically significant.Furthermore, all five intervention methods significantly downregulated the expression levels of SREBP-1c and FAS genes in the liver Srebp-1 pathway (P < 0.01). Conclusions:Intermittent fasting combined with Ling-gui-zhu-gan decoction and prebiotics can improve NAFLD by regulating the gut microbiota and the SREBP-1 pathway, with the combined intervention showing more significant therapeutic effects. |
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