title: 4‑Phenylbutyrate protects rat skin flaps against ischemia‑reperfusion injury and apoptosis by inhibiting endoplasmic reticulum stress.
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.
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Zhen-Shuang
authors.initials: ZS
authors.lastname: Yue
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Lin-Ru
authors.initials: LR
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Ren-Fu
authors.initials: RF
authors.lastname: Quan
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Yang-Hua
authors.initials: YH
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qu
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Can-Da
authors.initials: CD
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Fang-Bing
authors.initials: FB
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, Zhejiang 311201, P.R. China.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D010654:Phenylbutyrates / Q000008:administration & dosage*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D010654:Phenylbutyrates; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C075773:4-phenylbutyric acid