Abstract
4‑phenylbutyrate (4‑PBA) is a low molecular weight fatty acid, which has been demonstrated to regulate endoplasmic reticulum (ER) stress. ER stress‑induced cell apoptosis has an important role in skin flap ischemia; however, a pharmacological approach for treating ischemia‑induced ER dysfunction has yet to be reported. In the present study, the effects of 4‑PBA‑induced ER stress inhibition on ischemia‑reperfusion injury were investigated in the skin flap of rats, and transcriptional regulation was examined. 4‑PBA attenuated ischemia‑reperfusion injury and inhibited cell apoptosis in the skin flap. Furthermore, 4‑PBA reversed the increased expression levels of two ER stress markers: CCAAT/enhancer-binding protein‑homologous protein and glucose‑regulated protein 78. These results suggested that 4‑PBA was able to protect rat skin flaps against ischemia‑reperfusion injury and apoptosis by inhibiting ER stress marker expression and ER stress‑mediated apoptosis. The beneficial effects of 4‑PBA may prove useful in the treatment of skin flap ischemia‑reperfusion injury.