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Updated: Dec 29, 2025
A Model of Chronic Nutrient Infusion in the Rat
Published on: August 14, 2013
Exogenous Secretin Improves Parenteral Nutrition-associated Liver Disease in Rats
Xuehui Cao1, Feng Feng2, Xuelai Liu1
1Pediatric Surgery Department.
Insights
Exogenous secretin improved liver health in rats with parenteral nutrition-associated liver disease. Secretin enhanced bile acid transport, potentially preventing intestinal failure-associated liver disease in patients receiving long-term TPN.
Area of Science:
- Hepatology
- Gastroenterology
- Neonatal Medicine
Background:
- Intestinal failure-associated liver disease (IFALD) is a severe complication in neonates receiving long-term total parenteral nutrition (TPN).
- Parenteral nutrition-associated liver disease (PNALD) poses significant risks, necessitating effective therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of exogenous secretin in a rat model of PNALD.
- To evaluate the effects of secretin on liver pathology and hepatic function in the context of TPN-induced liver injury.
Main Methods:
- Male Sprague-Dawley rats received 14-day continuous TPN.
- Rats were divided into three groups: Control, TPN, and TPN with daily exogenous secretin (2.5 nmol·kg⁻¹·day⁻¹).
- Liver and blood samples were analyzed after 14 days to assess liver function and histology.
Main Results:
- The TPN/Secretin group showed reduced direct bilirubin and liver total bile acid levels compared to the TPN group.
- Secretin treatment improved histological outcomes in the liver.
- Exogenous secretin enhanced canalicular bile acid transporter (BSEP) expression and inhibited basolateral transporters (OSTA, OSTB).
Conclusions:
- Secretin may ameliorate cholestasis in PNALD by modulating bile acid transport.
- Enhancing canalicular transport and inhibiting basolateral export of bile acids may decrease liver bile acid levels.
- Exogenous secretin presents a potential preventative and therapeutic option for IFALD in patients requiring long-term TPN.
Objectives:
Intestinal failure-associated liver disease (IFALD) is a feared and life-threatening complication in neonates with intestinal failure (IF) receiving long-term total parenteral nutrition (TPN). This study aims to investigate the effect of exogenous secretin on liver pathology and hepatic function in a rat model of PN-associated liver disease (PNALD).
Methods:
Male Sprague-Dawley rats underwent right jugular venous catheterization to receive 14-day continuous TPN therapy. All rats were allocated into 3 groups: the Control group (n = 8) did not have surgery or TPN and was fed standard rat chow ad libitum; the TPN group (n = 8) underwent catheter insertion and TPN treatment; and the TPN/S group (n = 8) also underwent catheter insertion, TPN treatment, and exogenous secretin treatment (2.5 nmol · kg · day) daily. Fourteen days after initial surgery, we collected the animals' liver and blood samples for further test.
Results:
The TPN/S group had diminished direct bilirubin (TPN, 2.1 ± 0.7 μmol/L; TPN/S, 1.5 ± 0.2 μmol/L) and liver total bile acid levels (TPN, 144.5 ± 21.2 μmol/L; TPN/S, 123.4 ± 10.4 μmol/L) and improved histological outcomes compared with those in the TPN group. Exogenous secretin also enhanced the canalicular transporter (BSEP, 0.5-fold, P = 0.011) and inhibited the basolateral transporter (OSTA, -0.48-fold, P = 0.002; OSTB, -0.6-fold, P = 0.013) of liver bile acid.
Conclusions:
In this animal model of PNALD, secretin may improve cholestasis by enhancing canalicular transport, inhibiting the basolateral export of liver bile acid, and eventually decreasing the total bile acid level in the liver. Exogenous secretin treatment may potentially prevent and treat IFALD in IF patients relying on long-term TPN therapy.
