Zhuang Qian, Ye Xin, Shen Shuang, Cheng Jinnian, Shi Yan, Wu Shan, Xia Jie, Ning Min, Dong Zhixia, Wan Xinjian
Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Front Pharmacol. 2021 Jul 1;12:701003. doi: 10.3389/fphar.2021.701003. eCollection 2021.
Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 () enzyme and was increased, whereas expression of adenosine triphosphate-binding cassette () transporters and was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.
胆固醇胆结石（CG）疾病与多种代谢异常有关。黄芪多糖（APS）已被证明对代谢紊乱具有多种益处。我们试图揭示APS对饮食诱导的小鼠CG形成的影响及其作用机制。给动物喂食普通饲料或致石饲料（LD），并添加或不添加APS。评估APS对CG形成的影响。通过液相色谱 - 串联质谱法测量胆囊胆汁和回肠中各胆汁酸（BAs）的水平。采用实时逆转录 - 定量聚合酶链反应和蛋白质印迹法评估参与BA代谢和肠肝循环的基因表达。收集盲肠内容物以表征微生物群谱。APS改善了LD诱导的小鼠CG形成。APS降低了胆囊胆汁中总胆固醇水平、胆汁酸疏水性指数和胆固醇饱和指数。APS的保护作用可能源于肠道中胆酸吸收减少和肝脏BA合成增加。APS减轻了LD诱导的肠道法尼醇X受体激活，并降低了回肠中成纤维细胞生长因子15的表达。在肝脏中，细胞色素P450（）酶和的表达增加，而三磷酸腺苷结合盒（）转运蛋白和的表达被APS降低。APS改善了肠道微生物群的多样性，并增加了拟杆菌门的相对丰度。APS对CG疾病具有明显益处，这可能与增强BA合成和改善肠道微生物群有关。我们的结果表明，APS可能是预防CG疾病的一种潜在策略。
