王敏 周璐 孙燕 陈琳 吴梦瑶 张鑫蕾 张淑静 高誉珊 杨佳敏 郑丰杰 李宇航

摘要 目的：對大柴胡汤及其“方剂要素”对NAFLD模型大鼠“肠-肝轴”作用机制进行相关分析，揭示大柴胡汤的配伍规律。方法：105只大鼠分为正常组、模型组、盐酸吡格列酮组、疏肝利胆组、健脾化痰组、通腑泄浊组、大柴胡汤组，按照方法造模及给药，检测“肝轴”及“肠轴”相关指标，采用Critic法进行综合评价。结果：与正常组比较，模型组“肝轴”以及“肠轴”各个指标权重之和Z总1、Z总2差异均有统计学意义（P<0.05）;与模型组比较，盐酸吡格列酮组、疏肝利胆组、通腑泄浊组以及大柴胡汤组“肝轴”各个指标权重之和Z总1差异均有统计学意义（P<0.05），盐酸吡格列酮组、健脾化痰组、通腑泄浊组以及大柴胡汤组“肠轴”各个指标权重之和Z总2差异有统计学意义（P<0.05）。肠道菌群分析显示，通腑泄浊方剂要素对改善NAFLD模型大鼠肠道菌群优势显著，能提高NAFLD大鼠肠道菌群中拟杆菌属、萨特氏菌属、假丁酸弧菌属细菌和Akkermansia muciniphila等有益菌的相对丰度。结论：大柴胡汤中疏肝利胆方剂要素主要通过疏利肝胆作用显著调节肝脏脂质代谢以及肝脏免疫功能，即调节“肝轴”;大柴胡汤中健脾化痰方剂要素主要通过健运脾胃、化痰作用改善肠黏膜屏障功能，即调节“肠轴”;大柴胡汤中通腑泄浊方剂要素主要调节肠道菌群;大柴胡汤全方则可同时作用于“肝轴”和“肠轴”，对NAFLD模型大鼠起治疗作用。

关键词 非酒精性脂肪性肝病;大柴胡汤;方剂要素;疏肝利胆;健脾化痰;通腑泄浊;肠-肝轴;CRITIC法;综合评价

Relevant Analysis of Dachaihu Decoction and its “Formula Elements” on the “Intesine-liver axis” in the NAFLD Model

WANG Min，ZHOU Lu，SUN Yan，CHEN Lin，WU Mengyao，ZHANG Xinlei，ZHANG Shujing，GAO Yushan，YANG Jiamin，ZHENG Fengjie，LI Yuhang

（School of Traditional Chinese Medicine，Beijing University of Chinese Medicine，Beijing 100029，China）

Abstract Objective：To observe the effects of Dachaihu Decoction and various “formula-factors” on action mechanism of “Intestine-liver axis” of NAFLD model and to reveal the compatibility rule of Dachaihu Decoction.Methods：A total of 105 rats were divided into a normal group，a model group，a Western medicine group，a Shugan Lidan Decoction group，a Jianpi Huatan group，a Tongfu Xiezhuo group and a Dachaihu decoction group.According to the method of modeling and administration，the relevant indexes of“liver axis”and“gut axis”were detected，and the comprehensive evaluation was carried out by the Critic method.Results：Compared with the normal group，in the model group，Z总1 、Z总2 of the sum of the weights of each index of“liver axis”and“gut axis”is statistically significant（P<0.05）.Compared with the model group，there were significant differences in the sum weight of Z总1 in liver axis in the Pioglitazone hydrochloride group，dispersing stagnated liver qi for promoting bile flow group，catharis and dispel turbidity group and the Dachaihu Decoction group.And there were significant differences in the sum weight of Z总2 in the Pioglitazone hydrochloride group，dispersing stagnated liver qi for promoting bile flow group，Catharis and dispel turbidity group and the Dachaihu Decoction group.The analysis of intestinal flora showed that Tongfu Xiezhuo Formula have significant advantages in improving intestinal flora of NAFLD model rats.It can increase the relative abundance of beneficial bacteria in intestinal flora of NAFLD rats，such as Bacteroides，Sartoria，Vibrio pseudobutyricum and Akkermansia muciniphila.Conclusion：Formula factors of“Shugan Lidan formula”mainly regulate lipid metabolism of liver and liver immune function，namely，regulating“liver axis”.The Jianpi Huatan Formula factors of the prescription mainly improves intestinal mucosal barrier function-that is，regulating the“intestinal axis”.The Tongfu Xiezhuo formula factors of the Dachaihu Decoction can regulate intestinal flora; Dachaihu Decoction can act on both“liver axis”and“intestinal axis”at the same time，and has therapeutic effects on NAFLD model rats.

Keywords Nonalcoholic fatty liver disease; Dachaihu Decoction; Formula factors; Dispersing stagnated liver qi for promoting bile flow; Invigorate the spleen and dissapte phlegm; Catharis and dispel turbidity; Intestinal-liver shaft; CRITIC method; Comprehensive evaluation

中图分类号：R242文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.03.012

非酒精性脂肪性肝病（Nonalcoholic Fatty Liver Disease，NAFLD）是一种与胰岛素抵抗（IR）和遗传易感密切相关的代谢应激性肝脏损伤，其病理学改变与酒精性肝病（ALD）相似，但患者无过量饮酒史，疾病谱包括非酒精性单纯性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）及其相关肝硬化和肝细胞癌[1]。随着人们生活方式和饮食结构的改变，NAFLD的患病率呈现逐年上升趋势，全球NAFLD患病率约为25.24%。其中北美洲24.1%、欧洲23.7%、亚洲27.4%、中东31.8%、非洲13.5%、南美洲30.5%[2]。虽然NAFLD由单纯脂肪肝发展为非酒精性脂肪性肝炎、肝硬化的时限很长，但由于其代谢紊乱、血脂升高，与心脑血管疾病的发展密切相关，对人类健康构成严重威胁，现在也越来越引起人们的重视，成为21世纪我国乃至全球重要的公共健康问题之一。

NAFLD在单纯脂肪肝或肝炎早期多无明显症状，现代临床多采用调节生活节奏，调整饮食习惯以及加强锻炼等方式加以干预，中医药在其治疗上有明显优势。……