中药干预非酒精性脂肪性肝炎的机制研究进展

梁欣宇; 林素琴; 王一斌; 徐静宜; 刘雅萌; 谢岑

doi:10.14148/j.issn.1672-0482.2023.0384

中药干预非酒精性脂肪性肝炎的机制研究进展

doi: 10.14148/j.issn.1672-0482.2023.0384

梁欣宇^{1, 2,},
林素琴^{1, 2},
王一斌²,
徐静宜^{1, 2},
刘雅萌^2, ,,
谢岑^{1, 2, ,}

1.
南京中医药大学新中药学院, 江苏南京 210023
2.
中国科学院上海药物研究所药物研究国家重点实验室, 上海 200120

基金项目:

国家自然科学基金优秀青年科学基金项目 82222071

国家自然科学基金青年科学基金项目 82104261

详细信息

作者简介:
梁欣宇, 女, 硕士研究生, E-mail: liangxinyu@simm.ac.cn

通讯作者:
谢岑, 女, 研究员, 博士生导师, 主要从事组织器官互作研究，E-mail: xiecen@simm.ac.cn

刘雅萌, 女, 副研究员, 主要从事肠道微生态调控研究，E-mail: yameng_liu@simm.ac.cn

中图分类号: R285.5
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- 被引次数: 0
出版历程
- 收稿日期: 2022-12-11
- 网络出版日期: 2023-04-17
- 发布日期: 2023-04-10

Research Progress on the Mechanism of Traditional Chinese Medicine in the Intervention of Nonalcoholic Steatohepatitis

LIANG Xin-yu^{1, 2
,},
LIN Su-qin^{1, 2},
WANG Yi-bin²,
XU Jing-yi^{1, 2},
LIU Ya-meng^{2
, ,},
XIE Cen^{1, 2
, ,}

1.
New School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
2.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai 200120, China

摘要

摘要: 非酒精性脂肪性肝病(Nonalcoholic fatty liver disease, NAFLD) 属于代谢综合征, 已成为一个普遍关注的公共卫生问题。非酒精性脂肪性肝炎(Nonalcoholic steatohepatitis, NASH)是NAFLD的进展性病变, 是由多种风险因素和多种组织器官平行相互作用的结果。由于NASH的潜在病理生理机制十分复杂, 目前还没有获批的药物来控制疾病的发生发展。中医将NAFLD归为“肝癖”范畴, 并将NASH分为肝郁脾虚、痰湿内阻、湿热蕴结及痰瘀互结4个证型。中医以其独特的理论体系和治疗策略, 可以对不同NASH症型进行有效干预和治疗。随着现代药理学和分子生物学的不断发展, 越来越多的研究表明中药复方和单味中药活性成分通过多种机制改善NASH, 从而推进了中医药的应用。为此该文分别从中药复方和单味中药活性成分这两方面重点论述了中药改善NASH的相关机制, 以期为合理有效治疗NASH提供理论和实验研究依据。
- 非酒精性脂肪性肝炎 /
- 中药复方 /
- 中药活性成分 /
- 机制研究
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome that has become a public health problem of general concern. Nonalcoholic steatohepatitis (NASH) is a progressive NAFLD lesion resulting from the interaction of multiple risk factors with multiorgan involvement. Due to the complex underlying pathophysiologic mechanisms that contribute to the development and progression of NASH, there are no approved drugs to control the progression of the disease. Based on traditional Chinese medicine(TCM) theory, NAFLD belongs to the category of "Ganpi", and was divided into 4 syndrom types: liver stagnation and spleen deficiency, internal obstruction of phlegm and dampness, obstruction of dampness and heat, and interaction of phlegm and blood stasis. Chinese medicine can effectively intervene and treat different clinical types of NASH with its unique theoretical system and treatment strategy. With the continuous development of modern pharmacology and molecular biology, more and more studies have shown that TCM compound formula and active monomers can improve NASH through various mechanisms, which promotes the application of TCM. This review focuses on the mechanisms related to the improvement of NASH by TCM from the perspectives of compound formula and active monomers, in order to provide a theoretical and experimental research basis for the rational and effective treatment of NASH.
- nonalcoholic steatohepatitis /
- traditional Chinese medicine compound formula /
- traditional Chinese medicine active monomers /
- mechanism study

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表 1 中药复方治疗NASH的相关机制

Table 1. Related mechanisms of traditional Chinese medicine compound formula in the treatment of NASH

功效	复方中药	治疗NASH的相关机制
疏肝健脾	健脾疏肝方逍遥散健脾化浊消脂方理中汤四逆散柴胡疏肝散	抑制NF-κB的表达; 增加L-FABP表达; 改善线粒体和内质网的功能^[9-11]。调节TLR4/TRIF炎性信号转导通路的活性; 调节肠道菌群^[12-16]。抑制肠源性毒素的吸收^[17-18]。抑制IKK/IKB/NF-κB信号通路的活化; 改善Keap1/Nrf2/ARE信号通路^[19-21]。改善脂代谢紊乱; 改善胰岛素抵抗; 保护肝细胞; 改善心理压力^[22-23]。上调脂联素的表达, 下调瘦素的表达; 调节IRE-1α/NF-κB通路^[24-25]。
化痰祛湿	化痰祛湿活血方降脂平肝汤茵陈二陈汤	活化ADPN/PI3K/AKT信号通路^[26-28]。抑制TLR4/TRIF炎性信号转导通路^[29]。抑制JNK1/AP-1通路^[30-31]。
清热利湿	葛根芩连汤清肝化痰活血方	抑制TLR4信号通路, 调节肠道菌群^[32-34]。调节LXRa/FAS信号通路^[35]。
活血化瘀	下瘀血汤祛痰活血方行气活血祛湿方益气补肾调脂方	抑制NLRP6的下调; 抑制NLRP3炎症小体; 降低血管新生相关基因的表达^[36-39]。抑制TLR4/NF-κB信号通路^[40-41]。抑制STING-IRF3信号转导通路^[42-43]。改善氧化应激; 改善肝脏的内质网应激; 改善细胞衰老^[44-47]。

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表 2 单味中药活性成分改善NASH的相关机制

Table 2. Related mechanism of single Chinese medicine active monomers in the improvement of NASH

中药活性成分	结构式	来源	改善NASH的相关机制
天麻素		天麻根茎	激活AMPKα信号传导^[48-52]。
白藜芦醇		葡萄、浆果、红酒	激活Nrf2/ARE信号通路; 调控胆汁酸代谢谱, 激活胆汁酸受体; 上调SIRT3的表达; 调节mmu-miR-599/PXR通路; 被肠道菌群转化为小分子代谢物^[53-59]。
竹节参总皂苷		竹节参	调节miR-199a-5p/ATG5信号通路; 调节miR-17-5p/MFN2信号通路^[60-64]。
大黄素		大黄、何首乌、虎杖	调节PI3K/AKT/NF-κB信号传导通路; 改善IRS-2/PI3K/AKT通路^[65-67]。
槲皮素		芦荟	调节PI3K/AKT/NF-κB信号通路^[67-71]。
苦参碱		苦参	改善内质网应激^[72-73]。
虫草素		蛹虫草	调节巨噬细胞极化; 抑制NF-κB和NLRP3炎性体激活; 激活AMPK信号通路^{[1, 74-80]}。
小檗碱		黄连根茎	调控ATF6/SREBP-1c途径; 调节肠道菌群; 改善胆汁酸稳态^[81-91]。

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中药干预非酒精性脂肪性肝炎的机制研究进展

doi: 10.14148/j.issn.1672-0482.2023.0384

作者简介:
梁欣宇, 女, 硕士研究生, E-mail: liangxinyu@simm.ac.cn

通讯作者:
谢岑, 女, 研究员, 博士生导师, 主要从事组织器官互作研究，E-mail: xiecen@simm.ac.cn

刘雅萌, 女, 副研究员, 主要从事肠道微生态调控研究，E-mail: yameng_liu@simm.ac.cn

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Research Progress on the Mechanism of Traditional Chinese Medicine in the Intervention of Nonalcoholic Steatohepatitis

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中药干预非酒精性脂肪性肝炎的机制研究进展

doi: 10.14148/j.issn.1672-0482.2023.0384

作者简介: 梁欣宇, 女, 硕士研究生, E-mail: liangxinyu@simm.ac.cn

通讯作者: 谢岑, 女, 研究员, 博士生导师, 主要从事组织器官互作研究，E-mail: xiecen@simm.ac.cn 刘雅萌, 女, 副研究员, 主要从事肠道微生态调控研究，E-mail: yameng_liu@simm.ac.cn

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Research Progress on the Mechanism of Traditional Chinese Medicine in the Intervention of Nonalcoholic Steatohepatitis

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出版历程

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作者简介:
梁欣宇, 女, 硕士研究生, E-mail: liangxinyu@simm.ac.cn

通讯作者:
谢岑, 女, 研究员, 博士生导师, 主要从事组织器官互作研究，E-mail: xiecen@simm.ac.cn

刘雅萌, 女, 副研究员, 主要从事肠道微生态调控研究，E-mail: yameng_liu@simm.ac.cn