Berberine prevents progression from hepatic steatosis to steatohepatitis and fibrosis by reducing endoplasmic reticulum stress.
Berberine prevents progression from hepatic steatosis to steatohepatitis and fibrosis by reducing endoplasmic reticulum stress.
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小檗碱通过减少内质网应激来防止肝脂肪变性发展为脂肪性肝炎和纤维化
DOI：
10.1038/srep20848
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发表时间：
2016-02-09
影响因子：
4.6
通讯作者：
Ning G
中科院分区：
文献类型：
--
作者：
Zhang Z;Li B;Meng X;Yao S;Jin L;Yang J;Wang J;Zhang H;Zhang Z;Cai D;Zhang Y;Ning G
非酒精性脂肪性肝病（NAFLD）的组织学范围从肝脂肪变性到脂肪性肝炎和纤维化。小檗碱（BBR）因其对肥胖、高血糖和血脂异常的治疗作用而闻名；然而，其对NAFLD的影响尚未被彻底探索。Db/ Db小鼠和蛋氨酸-胆碱缺乏小鼠灌胃BBR。我们发现BBR处理的小鼠比载药处理的小鼠更能抵抗肝脏脂肪变性，并且BBR显著减少肝脏炎症、纤维化和脂质过氧化物。BBR的有益作用与抑制内质网（ER）应激有关。此外，BBR可降低原代肝细胞和肝细胞细胞系游离脂肪酸诱导的脂质积累和tunicamycin诱导的内质网应激。我们证明了BBR在体外表现出伴侣活性，减少了蛋白质聚集，并减轻了tunicamycin诱导的甘油三酯和胶原沉积。最后，我们发现BBR可以通过ATF6/SREBP-1c途径在体外逆转内质网应激激活的脂肪生成。这些结果表明，BBR可能是治疗肝脂肪变性和非酒精性脂肪性肝炎的新策略。
The histological spectrum of nonalcoholic fatty liver diseases (NAFLD) ranges from hepatic steatosis to steatohepatitis and fibrosis. Berberine (BBR) is known for its therapeutic effect on obesity, hyperglycaemia and dyslipidaemia; however, its effect on NAFLD has yet to be thoroughly explored. Db/db mice and methionine-choline-deficient diet-fed mice were administered BBR via gavage. We found that BBR-treated mice were more resistant to steatosis in the liver than vehicle-treated mice and that BBR significantly reduced hepatic inflammation, fibrosis and lipid peroxides. The beneficial effect of BBR was associated with suppressing endoplasmic reticulum (ER) stress. Additionally, BBR decreased the free fatty acid-induced lipid accumulation and tunicamycin-induced ER stress in primary hepatocytes and hepatocyte cell lines. We demonstrated that BBR exhibited chaperone activity, reduced protein aggregation in vitro and alleviated tunicamycin-induced triglyceride and collagen deposition in vivo. Finally, we showed that BBR could reverse ER stress-activated lipogenesis through the ATF6/SREBP-1c pathway in vitro. These results indicated that BBR may be a new therapeutic strategy against hepatic steatosis and non-alcoholic steatohepatitis.