Hepatic Overexpression of GRP94 in a Rabbit Model of Parenteral Nutrition-Associated Liver Disease.

Xueping Zhu,Yumin Xu,Jian Wang,Lingling Yu,Xing Feng,Xiaomin Zhang

doi:10.1155/2015/269831

Abstract

Objective. To use a rabbit model of parenteral nutrition-associated liver disease (PNALD) to study changes of the endoplasmic reticulum stress (ERS) marker glucose regulatory protein 94 (GRP94) and determine its role in the pathogenesis of PNALD. Methods. A rabbit PNALD model total parenteral nutrition (TPN) group was established. A corresponding control group received breast-feeding for one week. Serum biochemical parameters were measured and liver histological examinations were performed. The level of GRP94 mRNA and protein were measured. Results. The results showed that the serum TBIL, DBIL, and γ-GT levels in the TPN group were significantly higher than those in the control group, while levels of serum ALB in TPN group were significantly lower than those in the control group. The immunohistochemistry results showed that the protein expression level of GRP94 in the liver of TPN group was significantly increased compared with the control group. The RT-PCR results showed that the level of GRP94 mRNA in the liver of the TPN group was significantly higher compared with the control group. Conclusions. The mRNA and protein levels of GRP94 in the TPN group were both significantly increased, indicating that ERS may be directly related to the occurrence and development of PNALD.

Highlights

Parenteral nutrition has brought about a revolutionary improvement in the care of neonates with growth failure due to intestinal dysfunction
Parenteral nutrition-related liver disease (PNALD) is one of the most serious complications of neonatal parenteral nutrition-associated liver disease, which usually presents with steatosis, cholestasis, and elevated aminotransferases
Children born prematurely are more likely to suffer from total parenteral nutrition-associated cholestasis (PNAC) [3, 4] and even severe life-threatening cirrhosis

Summary

Introduction

Parenteral nutrition has brought about a revolutionary improvement in the care of neonates with growth failure due to intestinal dysfunction. Long-term (>2 weeks) parenteral nutrition is associated with a number of problems. Parenteral nutrition-related liver disease (PNALD) is one of the most serious complications of neonatal parenteral nutrition-associated liver disease, which usually presents with steatosis, cholestasis, and elevated aminotransferases. It has been reported [2] that about 30%–60% of children on long-term parenteral nutrition develop PNALD. Children born prematurely are more likely to suffer from total parenteral nutrition-associated cholestasis (PNAC) [3, 4] and even severe life-threatening cirrhosis. Despite the seriousness of the disease, the specific etiology and pathogenesis remains unclear

Methods

Results

Conclusion