Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway

Jin,Qianheng; Ju,Jihui; Xu,Lei; Liu,Yuefei; Li,Zhimin; Fu,Yi; Hou,Ruixing

doi:10.3892/mmr.2017.6708

Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway

Authors:
- Qianheng Jin
- Jihui Ju
- Lei Xu
- Yuefei Liu
- Zhimin Li
- Yi Fu
- Ruixing Hou
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Affiliations: Institute of Hand Surgery, Ruihua Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215100, P.R. China, Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215100, P.R. China
Published online on: June 7, 2017 https://doi.org/10.3892/mmr.2017.6708
Pages: 1472-1478

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Abstract

Previous studies have suggested that estradiol can reduce the ischemia/reperfusion (I/R) injury in skin flaps. However, the mechanism, particularly the signal pathways involved in this protective effect are not well established. In the current study, an I/R injury model was established in rats to explore the connection between estradiol protection during I/R injury and extracellular signal‑regulated kinase (ERK) signaling. Healthy male Wistar rats were divided into five groups (n=10): Control group (group I), I/R group (group II), saline group (group III), estradiol group (group IV) and inhibitor (PD‑98059) group (group V). The survival rate of the flap was compared between groups, morphological changes were observed by hematoxylin and eosin staining of sections, and terminal deoxynucleotidyl transferase dUTP nick end labeling was performed to identify apoptotic cells and determine the apoptotic index. To further investigate the mechanism, western blot analysis was performed to assess the protein level of ERK1/2, phospho‑ERK1/2, and mitogen‑activated protein kinase phosphatase 1 (MKP‑1). The results of the present study demonstrated that estradiol therapy can reduce I/R injury and decrease the apoptosis index in an axial skin flap model. The inhibitor of the ERK pathway (PD‑98059) partially abolished the effects of estradiol, which involve the phosphatase enzyme MKP‑1. Taken together, the findings of the present study indicate that estradiol may act by reducing the expression of MKP‑1, mediating the expression/activation changes of the ERK pathway and subsequently reduce the level of apoptosis and the I/R injury the axial flap. Estrogen may be used to mitigate the adverse reaction caused by ischemia‑reperfusion injury and effectively improve the survival rate and survival quality of free skin flap and improve patient prognosis.

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