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04.01.2019 | Original Article

4-Phenylbutyric Acid Attenuates Endoplasmic Reticulum Stress-Mediated Intestinal Epithelial Cell Apoptosis in Rats with Severe Acute Pancreatitis

verfasst von: Yun-dong You, Wen-hong Deng, Wen-yi Guo, Liang Zhao, Fang-chao Mei, Yu-pu Hong, Yu Zhou, Jia Yu, Sheng Xu, Wei-xing Wang

Erschienen in: Digestive Diseases and Sciences | Ausgabe 6/2019

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Abstract

Objectives

The present study aimed to determine whether intestinal epithelial cell (IECs) apoptosis could be induced by endoplasmic reticulum stress (ERS) in severe acute pancreatitis (SAP), and the role of chemical chaperone 4-phenylbutyric acid (4-PBA) in SAP-associated intestinal barrier injury.

Methods

Twenty-four male Sprague Dawley rats were randomly divided into three groups: the sham operation group, the SAP group, and the SAP model plus 4-PBA treatment group (4-PBA group). A rat model of SAP was induced by retrograde injection of 5% sodium taurocholate (STC) into the biliopancreatic duct; in the 4-PBA group, 4-PBA was injected intraperitoneally at a dose of 50 mg/kg body weight for 3 days before modeling.

Results

The results indicated that 4-PBA attenuated the following: (1) pancreas and intestinal pathological injuries, (2) serum TNF-α, IL-1β, and IL-6, (3) serum DAO level, serum endotoxin level, (4) the apoptosis of IECs, (5) ER stress markers (caspase-12, CHOP, GRP78, PERK, IRE1α, ATF6) and caspase-3 expression in intestinal. However, the serum AMY, LIPA levels, and the expression of caspase-9, caspase-8 were just slightly decreased.

Conclusions

ERS may be considered a predominant pathway, which is involved in the apoptosis of IECs during SAP. Furthermore, 4-PBA protects IECs against apoptosis in STC-induced SAP by attenuating the severity of ERS.

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Titel: 4-Phenylbutyric Acid Attenuates Endoplasmic Reticulum Stress-Mediated Intestinal Epithelial Cell Apoptosis in Rats with Severe Acute Pancreatitis
verfasst von: Yun-dong You
Wen-hong Deng
Wen-yi Guo
Liang Zhao
Fang-chao Mei
Yu-pu Hong
Yu Zhou
Jia Yu
Sheng Xu
Wei-xing Wang
Publikationsdatum: 04.01.2019
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 6/2019
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-018-5437-1

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