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

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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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Acknowledgments

This study was supported by National Natural Science Foundation of China (Nos. 81370562, 81360081), the National Natural Science Foundation Youth Project (Grant No. 81500488), and the Independent Research Project of Wuhan University (No. 2042017kf0141).

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Author notes

  1. Yun-dong You and Wen-hong Deng have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei province, China

    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

  2. Key Laboratory of Hubei Province for Digestive System Disease, 9 Zhangzhidong Road, Wuhan, 430060, Hubei province, China

    Yun-dong You, Fang-chao Mei, Yu-pu Hong & Yu Zhou

  3. Central Laboratory, Renmin Hospital of Wuhan University, 9 Zhangzhidong Road, Wuhan, 430060, Hubei province, China

    Liang Zhao

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You, Yd., Deng, Wh., Guo, Wy. et al. 4-Phenylbutyric Acid Attenuates Endoplasmic Reticulum Stress-Mediated Intestinal Epithelial Cell Apoptosis in Rats with Severe Acute Pancreatitis. Dig Dis Sci 64, 1535–1547 (2019). https://doi.org/10.1007/s10620-018-5437-1

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