Dipeptidyl peptidase IV inhibitors reduce hepatic fibrosis and lipid accumulation in rat intestinal failure-associated liver disease models.

IF 1.5 3区医学 Q2 PEDIATRICS

Pediatric Surgery International Pub Date : 2024-10-29 DOI:10.1007/s00383-024-05863-1

Ryo Sueyoshi, Junya Ishii, Susumu Yamada, Marumi Kawakami, Kenji Tanabe, Osamu Segawa

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引用次数: 0

Abstract

Purpose: This study aimed to investigate the effectiveness of dipeptidyl peptidase IV inhibitors (DPP4-I) against liver damage, especially fibrosis and lipid accumulation, in a rat intestinal failure-associated liver disease (IFALD) model.

Methods: SD rats were divided into two groups: the Control (n = 7; normal saline + IFALD model) and DPP4-I (n = 7; DPP4-I + IFALD model; short bowel syndrome (SBS) + total parenteral nutrition) groups. All rats were euthanized 21 days postoperatively to obtain tissue samples. Liver fibrosis was evaluated by Sirius Red and α-SMA staining. Liver damage was assessed using the steatosis, activity, and fibrosis score. Inflammation cytokines were examined by ELISA.

Results: The survival rate was comparatively different, being 87.5% in the DPP4-I group and 70.0% in the Control group. Two rats of the Control group showed progressive liver fibrosis in the periportal area with fibrous streaks. Further, the mean area percentage of α-SMA immune-positive cells was significantly lower in the DPP4-I group than in the Control group. TGF-β levels were significantly lower in the DPP4-I group than in the Control group.

Conclusion: DPP4-I administration reduced liver fibrosis in IFALD, possibly by inhibiting DPP4-I-induced adipogenesis and suppressing TGF-β. These results may contribute to elucidating the mechanism of IFALD.

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二肽基肽酶 IV 抑制剂可减轻大鼠肠功能衰竭相关肝病模型中的肝纤维化和脂质蓄积。

目的：本研究旨在探讨二肽基肽酶IV抑制剂（DPP4-I）对大鼠肠功能衰竭相关肝病（IFALD）模型中肝脏损伤，尤其是肝纤维化和脂质蓄积的有效性：将 SD 大鼠分为两组：对照组（n = 7；正常生理盐水 + IFALD 模型）和 DPP4-I 组（n = 7；DPP4-I + IFALD 模型；短肠综合征 (SBS) + 全肠外营养）。所有大鼠在术后 21 天安乐死，以获取组织样本。肝纤维化通过天狼星红和α-SMA染色进行评估。肝脏损伤采用脂肪变性、活性和纤维化评分进行评估。用 ELISA 检测炎症细胞因子：DPP4-I组和对照组的存活率分别为87.5%和70.0%。对照组有两只大鼠的肝门周围区域出现进行性肝纤维化，并伴有纤维条纹。此外，DPP4-I 组 α-SMA 免疫阳性细胞的平均面积百分比明显低于对照组。DPP4-I组的TGF-β水平明显低于对照组：结论：服用DPP4-I可减轻IFALD患者的肝纤维化，这可能是通过抑制DPP4-I诱导的脂肪生成和抑制TGF-β实现的。这些结果可能有助于阐明 IFALD 的发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Surgery International 医学-外科

CiteScore

3.00

自引率

5.60%

发文量

215

审稿时长

3-6 weeks

期刊介绍： Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children. The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include: -Review articles- Original articles- Technical innovations- Letters to the editor