研究动态
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依据非酒精性脂肪性肝炎小鼠模型,研究Elobixibat对肝肿瘤、微生物组和胆酸水平的影响。

Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis.

发表日期:2023 Sep 04
作者: Yoshiaki Sugiyama, Kenta Yamamoto, Takashi Honda, Asuka Kato, Hisanori Muto, Shinya Yokoyama, Takanori Ito, Norihiro Imai, Yoji Ishizu, Masanao Nakamura, Tomomi Asano, Atsushi Enomoto, Kei Zaitsu, Masatoshi Ishigami, Mitsuhiro Fujishiro, Hiroki Kawashima
来源: Hepatology International

摘要:

提高的胆汁酸水平与脂肪肝中的肝肿瘤有关。癫痫症胱切肠胆汁酸转运蛋白抑制剂可能抑制远端回肠中的胆汁酸吸收,并增加结肠中的胆汁酸水平,潜在降低血清和肝脏胆汁酸水平。本研究旨在调查这些因素对肝肿瘤的影响。C57BL/6J小鼠通过一次腹腔注射25mg/kg二乙基亚硝胺接种。它们从8周龄开始饲喂缺乏胆碱的高脂饮食,同时给予或不给予愛樂美胆碱(EA Pharma,日本东京)处理。两组小鼠均显示肝脏脂肪积累和纤维化,两组之间无显著差异。然而,愛樂美胆碱处理组的小鼠显示出更少的肝肿瘤。愛樂美胆碱处理后,血清总胆汁酸水平(包括游离、牛磺酸结合、醇甙结合以及牛磺-α/β-胆汁酸)显著降低。愛樂美胆碱处理组的粪便中革兰阳性细菌的比例(5.4%)明显低于无愛樂美胆碱处理组(33.7%)。愛樂美胆碱通过抑制胆汁酸重吸收,降低血清和肝脏中的总胆汁酸和原生胆汁酸水平来抑制肿瘤生长。此外,结肠中存在的胆汁酸可能导致革兰阳性细菌比例的显著降低,从而潜在地导致二次胆汁酸合成的减少。 © 2023. 亚太肝病研究协会.
Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor.C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20 weeks starting from 8 weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan).Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/β-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%).Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption, and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.© 2023. Asian Pacific Association for the Study of the Liver.