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黄连温胆汤干预代谢相关脂肪性肝病脂质堆积的作用机制
DOI: 10.12449/JCH260522
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：姚康萌负责设计论文框架，拟定写作思路，起草论文；张馨日负责搜集相关文献；郎轶萱负责论文修改；冷炎负责指导撰写文章并最后定稿。姚康萌和张馨日对本文贡献等同，同为第一作者。
Mechanism of action of Huanglian Wendan decoction in treatment of lipid accumulation in metabolic dysfunction-associated fatty liver disease
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摘要: 代谢相关脂肪性肝病（MAFLD）的核心特征为肝脏脂质堆积，与脂质代谢紊乱、胰岛素抵抗及炎症反应等因素密切相关，而异常的脂质堆积又可加剧上述因素，从而进一步加重脂质堆积，形成恶性循环。黄连温胆汤在改善MAFLD脂质堆积方面展现出独特优势，但其作用机制较为复杂。本文结合最新文献证据，系统总结黄连温胆汤从调节脂质代谢、改善胰岛素抵抗和抗炎等3个方面改善脂质堆积的作用机制以及相关中药活性成分的药理作用，为黄连温胆汤治疗MAFLD的临床应用提供理论依据。Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） has the core pathological feature of liver lipid accumulation， which is closely associated with the factors such as lipid metabolism disorders， insulin resistance， and inflammation， and abnormal lipid accumulation can exacerbate these factors and further intensify lipid accumulation， thereby forming a vicious circle. Huanglian Wendan decoction has shown unique advantages in alleviating lipid accumulation associated with MAFLD， but its mechanism of action is relatively complex. With reference to the latest literature evidence， this article systematically summarizes the mechanism of action of Huanglian Wendan decoction in improving lipid accumulation by regulating lipid metabolism， ameliorating insulin resistance， and exerting an anti-inflammatory effect， as well as the pharmacological actions of related active components， in order to provide a theoretical basis for the clinical application of Huanglian Wendan decoction in the management of MAFLD.
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图 1 脂质堆积与其影响因素的作用关系
Figure 1. The interplay between lipid accumulation and contributing factors
注： PPARα，过氧化物酶体增殖物激活受体α；CPT1，肉碱棕榈酰转移酶1；LXRα，肝X受体α；ABCA1，三磷酸腺苷结合盒转运蛋白A1；CYP7A1，细胞色素P450家族7亚家族A成员1；SREBP-1c，固醇调节元件结合蛋白1c。
图 2 黄连温胆汤通过调节脂质代谢改善脂质堆积的作用机制
Figure 2. Mechanism by which Huanglian Wendan decoction improves lipid accumulation via lipid metabolism regulation
注： SCFA，短链脂肪酸；GPR41/43，G蛋白偶联受体41/43；GLP1，胰高血糖素样肽1；PYY，YY肽；PI3K/Akt，磷脂酰肌醇3-激酶/蛋白激酶B；FOXO1，叉头框蛋白O1；GLUT4，葡萄糖转运蛋白4。
图 3 黄连温胆汤通过胰岛素抵抗改善脂质堆积的作用机制
Figure 3. Mechanism by which Huanglian Wendan decoction reduces lipid accumulation via amelioration of insulin resistance
注： NLRP3，核苷酸结合寡聚结构域样受体家族热蛋白结构域相关蛋白3；Caspase-1，胱天蛋白酶1；TGR5，G蛋白偶联胆汁酸受体1；NF-κB，核因子κB；PPARα，过氧化物酶体增殖物激活受体α；TLR4，Toll样受体4；LPS，脂多糖。
图 4 黄连温胆汤通过抗炎改善脂质堆积的作用机制
Figure 4. Mechanism by which Huanglian Wendan decoction reduces lipid accumulation via anti-inflammatory action
表 1 黄连温胆汤主要活性成分的药理作用
Table 1. Pharmacological actions of the main active constituents of Huanglian Wendan decoction
活性成分 归属中药 靶点/通路/途径 具体效应 参考文献 半夏水提取物 半夏 ATGL↑ 促进脂质分解 ［39］ 荭草素 竹茹 PI3K/Akt↑，P38/MAPK↑，参与GLUT2转运 改善胰岛素抵抗 ［40-41］ 新橙皮苷、柚皮苷 枳实 NF-κB↓ 抗炎 ［42］ 茯苓提取物 茯苓 PPARα↑，SREBP-1c↓ 调节脂质代谢 ［43］ 甘草查尔酮A 甘草 NF-κB↓ 抗炎 ［44］ 姜辣素 生姜 PI3K/Akt↑ 改善胰岛素抵抗 ［45］ 小檗碱 黄连 SREBP-1c↓ 抑制脂质合成 ［16］ 注：ATGL，脂肪甘油三酯脂肪酶；PI3K，磷脂酰肌醇3-激酶；Akt，蛋白激酶B；P38/MAPK，促分裂原活化的蛋白质激酶；GLUT2，葡萄糖转运蛋白2；NF-κB，核因子κB；PPARα，过氧化物酶体增殖物激活受体α；SREBP-1c，固醇调节元件结合蛋白1c。
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