猪胆粉有效成分 HDCA 通过调控肠道胆汁酸代谢抑制胆固醇结石形成的实验研究

doi:10.12092/j.issn.1009-2501.2026.08.002

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (8): 1016-1026.doi: 10.12092/j.issn.1009-2501.2026.08.002

• 基础研究 • 上一篇

猪胆粉有效成分 HDCA 通过调控肠道胆汁酸代谢抑制胆固醇结石形成的实验研究

苏英洋¹^,²(), 邓妍¹, 刘星羽², 杜玉珍², 宁敏², 吴姗², 吴凯悦²^,*(), 沈双²^,³^,*()

1. 上海海洋大学水产与生命学院，上海 201306
2. 上海交通大学医学院附属第六人民医院，上海 201306
3. 上海健康医学院附属第六人民医院，上海 201306

收稿日期:2025-08-26 修回日期:2025-10-24 出版日期:2026-08-26 发布日期:2026-09-09
通讯作者: 吴凯悦,沈双 E-mail:17332515661@163.com;fuyou_1995@163.com;shuangshen.no.1@163.com
作者简介:苏英洋，女，硕士研究生，研究方向：胆固醇代谢与疾病。E-mail：17332515661@163.com
基金资助:
国家自然科学基金项目（82200710）；上海健康医学院校院协同合作重点项目（XJJJ2503-6）

Experimental study on the inhibition of cholesterol gallstone formation by HDCA, the active component of Pulvis Fellis Suis, through regulation of intestinal bile acid metabolism

Yingyang SU¹^,²(), Yan DENG¹, Xingyu LIU², Yuzhen DU², Min NING², Shan WU², Kaiyue WU²^,*(), Shuang SHEN²^,³^,*()

1. College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China
2. Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201306, China
3. Shanghai University of Medicine & Health Sciences Affiliated Sixth People^,s Hospital, Shanghai 201306, China

Received:2025-08-26 Revised:2025-10-24 Online:2026-08-26 Published:2026-09-09
Contact: Kaiyue WU,Shuang SHEN E-mail:17332515661@163.com;fuyou_1995@163.com;shuangshen.no.1@163.com

摘要/Abstract

摘要：

目的: 探究猪去氧胆酸（hyodeoxycholic acid，HDCA）通过调控肠道胆汁酸代谢，影响法尼醇X受体（farnesoid X receptor，FXR）活性，抑制胆固醇结石生成。方法: 将C57BL/6J小鼠随机分成对照组、胆固醇结石模型组、猪胆粉（pulvis fellis suis，PFS）（7%、10%）给药干预组，每组6只；将C57BL/6J小鼠随机分成对照组、胆固醇结石模型组、HDCA（0.1%、0.5%、1%）给药干预组，每组6只；对各组小鼠进行称重、拍照、收集各组织样本并进行胆囊结石等级评估；用总胆固醇（T-CHO）检测试剂盒和酶标仪检测样本中总胆固醇的含量；在体外细胞实验方面，通过实时定量聚合酶链反应（qPCR）分析HDCA对肠道细胞中FXR的直接调节作用；使用16S核糖体RNA（16S ribosomal RNA，16S rRNA）测序技术检测各组小鼠粪便菌群的变化差异；液相色谱-质谱法（liquid chromatography-mass spectrometry，LC-MS/MS）测定回肠组织中胆汁酸池的变化。结果: 与模型组相比，10%PFS和1%HDCA给药干预组均显著降低小鼠胆囊胆固醇结石等级和血清胆固醇含量（P<0.01），并且1%HDCA组显著降低小鼠肝重与体质量的比值和肝脏胆固醇含量（P<0.01）；在体外实验中，HDCA显著降低肠道细胞Caco-2中FXR的相对表达量（P<0.05、P<0.01）；HDCA显著降低疣微菌门（Verrucomicrobiota与激活FXR型胆汁酸呈显著正相关）的含量（P<0.05），显著升高拟杆菌门（Bacteroidota与激活FXR型胆汁酸呈显著负相关）的含量（P<0.01）；并且HDCA显著改变肠道胆汁酸成分，降低激活FXR型胆汁酸含量占比，升高抑制FXR型胆汁酸含量占比（P<0.05）。结论: HDCA可能通过调节肠道菌群提高抑制FXR型胆汁酸的含量，从而间接发挥抑制肠道FXR，促进胆汁酸合成且降低胆固醇饱和度的作用，达到抑制胆固醇结石形成的效果。

关键词: 猪去氧胆酸, 猪胆粉, 法尼醇X受体, 胆汁酸, 胆固醇结石

Abstract:

AIM: To explore how hyodeoxycholic acid (HDCA) regulates intestinal bile acid metabolism and thereby modulates the activity of farnesoid X receptor (FXR) to inhibit the formation of cholesterol gallstones. METHODS: The C57BL/6J mice were randomly divided into a control group, a cholesterol gallstone model group, and a Pulvis fellis suis (PFS) (7%, 10%) administration intervention group (6 mice in each group). The C57BL/6J mice were also randomly divided into a control group, a cholesterol gallstone model group, and HDCA (0.1%, 0.5%, 1%) administration intervention groups (6 mice in each group). The mice in each group were weighed, photographed, and tissue samples were collected for gallstone grade assessment. The total cholesterol (T-CHO) content in the samples was detected using a total cholesterol detection kit and a microplate reader. In the in vitro cell experiments, the direct regulatory effect of HDCA on FXR in intestinal cells was analyzed by quantitative polymerase chain reaction (qPCR). The differences in fecal microbiota among the groups were detected using 16S ribosomal RNA (16S rRNA) sequencing technology. The changes in the bile acid pool in the ileum tissue were determined by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Compared with the model group, both the 10% PFS and 1% HDCA intervention groups significantly reduced the grade of cholesterol gallstones in the gallbladder and the serum cholesterol content of mice (P<0.01), and the 1% HDCA group significantly decreased the ratio of liver weight to body weight and the cholesterol content in the liver of mice (P<0.01); in the in vitro experiments, HDCA significantly reduced the relative expression level of FXR in intestinal cells Caco-2 (P<0.05, P<0.01); HDCA significantly reduced the content of the Verrucomicrobiota (which was significantly positively correlated with activated FXR-type bile acids) (P<0.05) and significantly increased the content of the Bacteroidota (which was significantly negatively correlated with activated FXR-type bile acids) (P<0.01). Moreover, HDCA significantly changed the composition of intestinal bile acids, reducing the proportion of activated FXR-type bile acids and increasing the proportion of inhibitory FXR-type bile acids (P<0.05). CONCLUSION: HDCA may increase the inhibition of FXR-type bile acids by regulating the intestinal flora, thereby indirectly exerting the effect of inhibiting intestinal FXR, promoting bile acid synthesis and reducing cholesterol saturation, and achieving the goal of inhibiting the formation of cholesterol gallstones.

Key words: hyodeoxycholic acid, Pulvis Fellis Suis, farnesoid X receptor, bile acids, cholesterol gallstones

中图分类号:

R965.2

苏英洋, 邓妍, 刘星羽, 杜玉珍, 宁敏, 吴姗, 吴凯悦, 沈双. 猪胆粉有效成分 HDCA 通过调控肠道胆汁酸代谢抑制胆固醇结石形成的实验研究[J]. 中国临床药理学与治疗学, 2026, 31(8): 1016-1026.

Yingyang SU, Yan DENG, Xingyu LIU, Yuzhen DU, Min NING, Shan WU, Kaiyue WU, Shuang SHEN. Experimental study on the inhibition of cholesterol gallstone formation by HDCA, the active component of Pulvis Fellis Suis, through regulation of intestinal bile acid metabolism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1016-1026.

图/表 8

图 1

Fig.1 PFS has a significant preventive effect on cholesterol gallstones in mice ($ \overline{\text{x}} $±s, n=6) A: gallstone grades of the gallbladder in mice; B: incidence of gallstones in mice; C: body weight of mice before model induction; D: body weight of mice at model completion; E: appearance of the gallbladder in mice; F: ratio of liver weight to body weight in mice; G: total cholesterol content in mouse serum. *P<0.05; **P<0.01.

图 2

Fig.2 HDCA has a significant preventive effect on cholesterol gallstones in mice ($ \overline{\text{x}} $±s, n=6) A: gallstone grades of the gallbladder in mice; B: incidence of gallstones in mice; C: body weight of mice before model induction; D: body weight of mice at model completion; E: appearance of the gallbladder in mice; F: ratio of liver weight to body weight in mice; G: total cholesterol content in mouse serum; H: total cholesterol content in the liver. *P<0.05; **P<0.01.

图 3

Fig.3 HDCA inhibits the expression of FXR in intestinal Caco-2 cells ($ \overline{\text{x}} $±s, n=3). *P<0.05; **P<0.01.

图 4

Fig.4 The situation of the intestinal microbiota in mice after HDCA intervention ($ \overline{\text{x}} $±s, n=4) A: heat map showing the relationship between the intestinal microbiota and bile acids; B: composition of the microbial community in the intestinal microbiota; C-K: content of different phyla of microbiota in the intestine. *P<0.05; **P<0.01.

表 1

Table 1 The top 10 bile acids in content after HDCA intervention in mice

Bile acid	Content (nmol/g)	Effect on FXR
CA	5931.64	agonists
TCA	2601.21	agonists
HDCA	2598.39	antagonists
DCA	2087.83	agonists
LCA	1473.53	agonists
TDCA	1079.37	agonists
GCA	552.98	agonists
6-ketoLCA	224.95	agonists
beta-MCA	178.26	antagonists
alpha-MCA	120.80	antagonists

图 5

Fig.5 The content of different bile acids in mice after HDCA intervention ($ \overline{\text{x}} $±s, n=4) A-G: contents of FXR-activating bile acids; H-J: contents of FXR-inhibiting bile acids. *P<0.05; **P<0.01.

图 6

Fig.6 The bile acid conditions of activating or inhibiting FXR after HDCA intervention in mice ($ \overline{\text{x}} $±s, n=4) A: total FXR-activating bile acid content; B: total FXR-inhibiting bile acid content; C: proportion of FXR-activating/inhibiting bile acids. *P<0.05.

图 7

Fig.7 The enterohepatic circulation of bile acids

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猪胆粉有效成分 HDCA 通过调控肠道胆汁酸代谢抑制胆固醇结石形成的实验研究

Experimental study on the inhibition of cholesterol gallstone formation by HDCA, the active component of Pulvis Fellis Suis, through regulation of intestinal bile acid metabolism

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