Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Liver Disease Department, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, Zhejiang, 315010, China.
Medical School of Ningbo University, Ningbo, Zhejiang, 315211, China.
Biomed Pharmacother. 2020 Apr;124:109915. doi: 10.1016/j.biopha.2020.109915. Epub 2020 Jan 25.
BACKGROUND: Our previous studies found that salidroside can effectively treat non-alcoholic steatohepatitis (NASH). Here, we discuss the mechanism of salidroside in the treatment of NASH with a focus on the gut microbiota-bile acid-farnesoid X receptor axis. METHODS: A NASH mouse model was created by providing mice with a high-fat diet (HFD) for 14 weeks. Mice were randomly divided into the HFD group, HFD + salidroside treatment group, and HFD + obeticholic acid treatment group (n = 8 in each group) and were intragastrically administered corresponding drugs for 4 weeks. Hematoxylin-eosin staining was performed to evaluate the histopathological changes associated with the various treatments. In addition, liver triglyceride (TG) content, serum alanine aminotransferase (ALT) activity, serum inflammatory factors, gut microbiota diversity, and the bile acid profile were evaluated. Western blotting and RT-PCR were performed to detect the expressions of FXR and fibroblast growth factor 15 (FGF15). RESULTS: The HFD group displayed obvious signs of hepatic steatosis. The liver TG, serum ALT, and IL-1a, IL-12, MCP-1, KC, MIP-1a, and MIP-1β were significantly higher in the HFD group than the control group (P < 0.01). Intestinal bacteria and bile acid profiles changed significantly in the HFD group (P < 0.05). Further, the expressions of FXR and FGF15 decreased significantly in the HFD group (P < 0.05). After treatment with salidroside, liver steatosis, TG content, and serum inflammatory factors significantly improved and HFD-induced intestinal bacteria, bile acid disorder, and FXR deficiency were significantly alleviated (P < 0.05). CONCLUSION: Salidroside can improve NASH via the gut microbiota-bile acid-FXR axis.
背景：我们之前的研究发现，红景天苷可以有效治疗非酒精性脂肪性肝炎（NASH）。在这里，我们重点讨论了红景天苷通过肠道微生物群-胆汁酸-FXR 轴治疗 NASH 的机制。
方法：通过给予高脂肪饮食（HFD）14 周来建立 NASH 小鼠模型。将小鼠随机分为 HFD 组、HFD+红景天苷治疗组和 HFD+奥贝胆酸治疗组（每组 8 只），并分别给予相应的药物进行 4 周的胃内给药。通过苏木精-伊红染色来评估与各种治疗相关的组织病理学变化。此外，还评估了肝甘油三酯（TG）含量、血清丙氨酸氨基转移酶（ALT）活性、血清炎症因子、肠道微生物群多样性以及胆汁酸谱。通过 Western blot 和 RT-PCR 检测 FXR 和成纤维细胞生长因子 15（FGF15）的表达。
结果：HFD 组显示出明显的肝脂肪变性迹象。与对照组相比，HFD 组的肝 TG、血清 ALT 以及 IL-1a、IL-12、MCP-1、KC、MIP-1a 和 MIP-1β 显著升高（P<0.01）。HFD 组肠道细菌和胆汁酸谱发生了显著变化（P<0.05）。此外，FXR 和 FGF15 的表达在 HFD 组中显著降低（P<0.05）。用红景天苷治疗后，肝脂肪变性、TG 含量和血清炎症因子明显改善，HFD 诱导的肠道细菌、胆汁酸紊乱和 FXR 缺乏明显缓解（P<0.05）。
结论：红景天苷可以通过肠道微生物群-胆汁酸-FXR 轴改善 NASH。
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