Pediatric surgery international · 2024
Dipeptidyl peptidase IV inhibitors reduce hepatic fibrosis and lipid accumulation in rat intestinal failure-associated liver disease models.
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Sueyoshi Ryo, Ishii Junya, Yamada Susumu, Kawakami Marumi, Tanabe Kenji, Segawa Osamu
Аннотация
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.
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.