Therapeutic effect and mechanism of 4‑phenyl butyric acid on renal ischemia‑reperfusion injury in mice

Wang,Xinlei; Zhang,Yang; Wuyun,Kun; Gong,Haixia

doi:10.3892/etm.2021.11067

Therapeutic effect and mechanism of 4‑phenyl butyric acid on renal ischemia‑reperfusion injury in mice

Authors:
- Xinlei Wang
- Yang Zhang
- Kun Wuyun
- Haixia Gong
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: December 15, 2021 https://doi.org/10.3892/etm.2021.11067
Article Number: 144
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the effects and possible mechanism of 4‑phenylbutyric acid (4‑PBA) on renal ischemia‑reperfusion injury (RIRI) in mice. A RIRI model of HK‑2 cells was constructed using hypoxia/reoxygenation (H/R) treatment. Dexmedetomidine and 4‑PBA were used to treat the cells before and after modeling. Apoptosis and expression levels of cyclophilin D (CypD), cytochrome c, eukaryotic translation initiation factor 2α (eIF2α), glucose‑regulated protein 78 (GRP78), intercellular adhesion molecule (ICAM)‑1 and vascular adhesion molecule (VCAM)‑1 were measured using flow cytometry, western blotting and immunohistochemistry. The renal volume, weight and renal arterial resistance index (RRI) were determined using the renal ischemia model. Compared with untreated model cells, 4‑PBA treatment significantly decreased apoptosis and the expression levels of CypD, Cytochrome c, eIF2α and GRP78 in HK‑2 cells. There was no significant change in renal volume and weight after modeling, but RRI was significantly decreased after 4‑PBA treatments in the model. Western blotting and immunohistochemistry analysis demonstrated that 4‑PBA treatment also significantly decreased the expression of ICAM‑1 and VCAM‑1. Overall, 4‑PBA had a therapeutic effect on RIRI in mice. This protection may be mediated by decreasing the expression levels of CypD, Cytochrome c, eIF2α and GRP78, and subsequent reduction of cellular oxygen free radicals and apoptosis, leading to an alleviated endoplasmic reticulum stress response and RIRI.

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