Hepalatide ameliorated progression of nonalcoholic steatohepatitis in mice
Hepalatide ameliorated progression of nonalcoholic steatohepatitis in mice
复制标题
贺普拉肽可改善小鼠非酒精性脂肪性肝炎的进展
DOI：
10.1016/j.biopha.2020.110053
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发表时间：
2020
影响因子：
7.5
通讯作者：
Wu J.
中科院分区：
文献类型：
--
作者：
Liu X. J;Liu C;Zhu L. Y;Fan C. L;Niu C;Liu X. P;Liu H. L;Wu J.
没有FDA批准的药物可用于治疗非酒精性脂肪性肝炎（NASH）。由高脂肪/卡路里饮食以及饮用水中高果糖/葡萄糖（HFCD-HF/g）引起的NASH的16周。方法：雄性小鼠被随机分为4组：对照组（正常饮食），HFCD-HF/HFCD-HF/ G组，HFCD-HF/G加低剂量或高剂量的肝肽（20或60 mg/kg，LH或HH，S.C。从9到16周）。结果：与HFCD-HF/G-FED小鼠相比喂食HFCD-HF/G Plus LH或HH的小鼠的甘油三酸酯和HH的胆固醇水平改善了血清丙氨酸氨基转移酶的治疗HH组中禁食的血糖，血清胰岛素和HOMA胰岛素耐药性指数。在用HH处理的小鼠中，很少有血清胆汁酸增加。结论：肝肽有效缓解了病理过程，代谢特征，肝细胞增多症和损伤，胰岛素抵抗，胰岛素抵抗，在NASH的小鼠模型中停止了肝纤维化进展，很可能是通过增加的。血清胆汁酸。
No FDA-approved medications are available for the treatment of nonalcoholic steatohepatitis (NASH). The present study aimed to assess the effects of Hepalatide, a sodium taurocholate cotransporting polypeptide (NTCP) receptor-binding agent, on metabolic and histopathologic changes of a mouse model of NASH caused by high fat/calorie diet plus high fructose/glucose in drinking water (HFCD-HF/G) for 16 weeks.. Methods: Male mice were randomly divided into 4 groups: controls (normal diet), HFCD-HF/G group, HFCD-HF/G plus low or high dose of Hepalatide (20 or 60 mg/kg, LH or HH, s.c. from 9 to 16 weeks)..Results: Compared to HFCD-HF/G-fed mice, serum triglyceride and cholesterol levels in mice fed HFCD-HF/G plus LH or HH were decreased. The treatment with Hepalatide decreased serum alanine aminotransferase levels significantly. Liver histology and TUNEL staining showed that Hepalatide remarkably attenuated inflammation, hepatocellular steatosis and apoptosis. Hepalatide treatment decreased fasting blood glucose, serum insulin and HOMA insulin resistance index in the HH group. Moreover, Masson’s staining, semi-quantitative score of fibrosis, and hydroxyproline content demonstrated that Hepalatide mitigated fibrotic progression in this murine NASH model. Additionally, most components of liver and few serum bile acids were increased in mice treated with HH..Conclusion: Hepalatide effectively alleviated the pathological process, metabolic profile, hepatocellular steatosis and injury, insulin resistance, halted hepatic fibrotic progression in a mouse model of NASH, most likely through the increase of serum bile acids.