Department of Pediatric Surgery, Tokyo Women's Medical University, 8‑1 Kawada‑Cho, Shinjuku‑Ku, Tokyo, 162‑8666, Japan.
Tokyo Women's Medical University Institute for Comprehensive Medical Sciences, 8‑1 Kawada‑Cho, Shinjuku‑Ku, Tokyo, 162‑8666, Japan.
Pediatr Surg Int. 2024 Oct 29;40(1):281. doi: 10.1007/s00383-024-05863-1.
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.
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.
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.
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.
本研究旨在探讨二肽基肽酶 4 抑制剂（DPP4-I）在大鼠肠衰竭相关肝病（IFALD）模型中对肝损伤，特别是纤维化和脂质积累的作用。
SD 大鼠分为两组：对照组（n=7；生理盐水+IFALD 模型）和 DPP4-I 组（n=7；DPP4-I+IFALD 模型；短肠综合征（SBS）+全胃肠外营养）。所有大鼠均于术后 21 天处死以获取组织样本。通过天狼星红和α-SMA 染色评估肝纤维化。使用脂肪变性、活动度和纤维化评分评估肝损伤。通过 ELISA 检测炎症细胞因子。
DPP4-I 组的生存率为 87.5%，而对照组为 70.0%。对照组有 2 只大鼠在门脉周围区域出现进行性肝纤维化，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 TGF-β 水平明显低于对照组。
DPP4-I 给药可减轻 IFALD 中的肝纤维化，可能通过抑制 DPP4-I 诱导的脂肪生成和抑制 TGF-β 来实现。这些结果可能有助于阐明 IFALD 的发病机制。
