四妙方通过调节肝脏脂质代谢和肠道微生物群来减轻非酒精性脂肪性肝病。
Si Miao Formula attenuates non-alcoholic fatty liver disease by modulating hepatic lipid metabolism and gut microbiota.
作者信息
Han Ruiting, Qiu Huihui, Zhong Jing, Zheng Ningning, Li Bingbing, Hong Ying, Ma Junli, Wu Gaosong, Chen Linlin, Sheng Lili, Li Houkai
机构信息
Functional Metabolomics and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China.
Functional Metabolomics and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
出版信息
Phytomedicine. 2021 May;85:153544. doi: 10.1016/j.phymed.2021.153544. Epub 2021 Mar 10.
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with few therapeutic options available currently. Traditional Chinese Medicine (TCM) has been practiced for thousands of years in China and Asian countries, and regarded as an important source for identifying novel medicines for diseases. Si Miao Formula (SMF) is a classical TCM formula for the treatment of gout disease by reducing serum uric acid concentrations, while high concentration of uric acid is also an independent risk factor for NAFLD.
PURPOSE
To investigate the protective effect of SMF on NAFLD in a mouse model induced by a high fat/high sucrose (HFHS) diet.
METHODS
Mice received a HFHS diet over a 16-week period to induce NAFLD with or without SMF intervention. Lipid levels were measured in both the liver and serum. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Liver transcriptomics was used to enrich differentially expressed genes and to predict regulatory pathways after gene set enrichment analysis. 16S rRNA gene sequencing was used to determine the microbial composition. Genes of liver lipid metabolism, inflammation and intestinal tight junctions were detected by qRT-PCR analysis.
RESULTS
SMF attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, improved sensitivity to insulin and also tolerance to glucose, in mice fed an HFHS diet. Hepatic transcriptomics showed that SMF downregulated the biosynthesis of fatty acids and stimulated the insulin secretion pathway. SMF significantly altered the gut microbiota composition and in particular increased the proportion of Akkermansia muciniphila. In agreement with liver transcriptomics, SMF downregulated the expression of genes implicated in the metabolism of lipids (Acly, Fas, Acc, Scd-1) and pro-inflammatory cytokines (Il-1β, Nlrp-3) in the livers.
CONCLUSION
The results indicate that SMF attenuates HFHS diet-induced NAFLD and regulates hepatic lipid metabolism pathways. The anti-NAFLD effect of SMF was linked to modulation of the gut microbiota composition and in particular an increased relative abundance of Akkermansia muciniphila.
背景
非酒精性脂肪性肝病（NAFLD）是一种慢性肝病，目前可用的治疗选择很少。中医在中国和亚洲国家已经应用了数千年，被视为发现治疗疾病新药的重要来源。四妙方（SMF）是一种经典的中药方剂，通过降低血清尿酸浓度来治疗痛风疾病，而高尿酸也是NAFLD的一个独立危险因素。
目的
研究四妙方（SMF）对高脂/高糖（HFHS）饮食诱导的小鼠NAFLD模型的保护作用。
方法
小鼠在16周内接受HFHS饮食以诱导NAFLD，同时进行或不进行SMF干预。测量肝脏和血清中的脂质水平。采用组织病理学染色评估肝脏脂质积累程度。利用肝脏转录组学对差异表达基因进行富集，并在基因集富集分析后预测调控通路。采用16S rRNA基因测序确定微生物组成。通过qRT-PCR分析检测肝脏脂质代谢、炎症和肠道紧密连接相关基因。
结果
在喂食HFHS饮食的小鼠中，SMF减轻了肝脏脂肪变性，降低了体重增加和脂质浓度，提高了胰岛素敏感性以及葡萄糖耐受性。肝脏转录组学显示，SMF下调了脂肪酸的生物合成并激活了胰岛素分泌途径。SMF显著改变了肠道微生物群组成，特别是增加了嗜黏蛋白阿克曼氏菌的比例。与肝脏转录组学一致，SMF下调了肝脏中参与脂质代谢（Acly、Fas、Acc、Scd-1）和促炎细胞因子（Il-1β、Nlrp-3）的基因表达。
结论
结果表明，SMF减轻了HFHS饮食诱导的NAFLD，并调节了肝脏脂质代谢途径。SMF的抗NAFLD作用与肠道微生物群组成的调节有关，特别是嗜黏蛋白阿克曼氏菌相对丰度的增加。
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