药学学报, 2021, 56(10): 2802-2808
引用本文:
马钰捷, 余生兰, 李琴琴, 黄璐瑶, 杨莉, 王峥涛, 丁丽丽. 五味子乙素通过增强肠道黏膜屏障功能改善小鼠非酒精性脂肪性肝病的研究[J]. 药学学报, 2021, 56(10): 2802-2808.
MA Yu-jie, YU Sheng-lan, LI Qin-qin, HUANG Lu-yao, YANG Li, WANG Zheng-tao, DING Li-li. Schisandrin B improves non-alcoholic fatty liver disease by impacting intestinal mucosal barrier function[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2802-2808.

五味子乙素通过增强肠道黏膜屏障功能改善小鼠非酒精性脂肪性肝病的研究
马钰捷1, 余生兰1, 李琴琴1, 黄璐瑶1, 杨莉1,2, 王峥涛1,2, 丁丽丽1,2*
1. 上海中医药大学中药研究所, 中药标准化教育部重点实验室暨国家中医药管理局中药新资源与质量评价重点实验室, 上海 201203;
2. 上海中药标准化研究中心, 上海 201203
摘要:
近年来,非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的患病率在我国大幅度提升,但临床上缺乏有效治疗药物。本文旨在探究五味子乙素(schisandrin B,SchB)对NAFLD的改善作用及其可能的作用机制。野生型C57BL/6J小鼠给予高脂高糖高胆固醇饲料(含40%脂肪、22%果糖、10%蔗糖和2%胆固醇)16周后诱导成NAFLD模型,使用SchB (120 mg·kg-1)口服治疗6周。通过检测体重、摄食量、葡萄糖耐量、胰岛素耐受、血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、谷丙转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate aminotransferase,AST)含量及肝脏病理学变化,评价SchB对小鼠NAFLD的改善作用。进一步检测血清脂多糖(lipopolysaccharide,LPS)含量、肠道渗透性及肠道黏膜屏障相关基因、蛋白的表达,同时分析盲肠内容物的肠道菌群组成及差异菌群,评价SchB改善NAFLD的潜在作用机制。实验方案经由上海中医药大学动物实验伦理委员会审查通过。本实验发现SchB在不改变摄食量的条件下显著减轻NAFLD小鼠的体重,降低血清中TC、ALT和AST的含量,减少肝脏的脂质堆积。同时,SchB改变NAFLD小鼠的肠道菌群组成,增加嗜黏蛋白阿克曼氏菌(Akkermansia muciniphilaA.muciniphila)的丰度,增加回肠和结肠中肠道黏膜屏障相关基因及蛋白的表达,维护肠道屏障稳态,从而缓解肝脏炎症。本研究表明,SchB通过调节肠道菌群结构和增强肠道黏膜屏障功能,从而减少肝脏脂质堆积、缓解炎症,改善NAFLD。
关键词:    五味子乙素      非酒精性脂肪性肝病      肠道菌群      肠道黏膜屏障      肝脏炎症     
Schisandrin B improves non-alcoholic fatty liver disease by impacting intestinal mucosal barrier function
MA Yu-jie1, YU Sheng-lan1, LI Qin-qin1, HUANG Lu-yao1, YANG Li1,2, WANG Zheng-tao1,2, DING Li-li1,2*
1. The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2. Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China
Abstract:
In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been dramatically increased in China and specific targeted therapy is still unavailable. The purpose of this research was to investigate whether schisandrin B (SchB) improves NAFLD and the potential mechanisms. Wildtype mice with C57BL/6J background were treated with special high fat diet (containing 40% fat, 22% fructose, 10% sucrose, and 2% cholesterol) for 16 weeks to induce NAFLD. Then SchB (120 mg·kg-1) were used to treat NAFLD mice for 6 weeks. Body weight, food intake, glucose tolerance, insulin resistance, serum level of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assayed and histopathological analysis were performed to evaluate the improvement of NAFLD induced by SchB. Furthermore, the level of lipopolysaccharide (LPS) in serum, intestinal permeability, and the expression of genes and proteins associated with mucosal defense were evaluated, intestinal flora composition in fresh cecal contents were analyzed and differential flora were identified to explore the potential mechanism. All animal experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. These results showed that SchB significantly reduced the body weight of NAFLD mice without changing food intake, and effectively reduced serum level of TC, ALT, and AST. SchB also significantly altered the composition of the microflora in NAFLD mice, increased the abundance of the Akkermansia muciniphila (A. Muciniphila) and elevated the expression of genes and proteins associated with the mucosal defense in ileum and colon, restored the permeability of intestinal barrier. In summary, SchB improves NAFLD by regulating the composition of the microflora and enhancing the function of intestinal barrier to further reduce the excessive lipids accumulation and hepatic inflammation.
Key words:    schisandrin B    non-alcoholic fatty liver disease    intestinal microflora    intestinal mucosal barrier    hepatic inflammation   
收稿日期: 2021-03-02
DOI: 10.16438/j.0513-4870.2021-0305
基金项目: 国家自然科学基金资助项目(81773961).
通讯作者: 丁丽丽,Tel:86-21-51322496,Fax:86-21-51322519,E-mail:nail8219@hotmail.com
Email: nail8219@hotmail.com
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