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

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.

D-allose alleviates ischemia/reperfusion (I/R) injury in skin flap via MKP-1

“…Choi, D. E. et al revealed that ERK activation was critical against renal I/R injury (Choi et al 2017). Jin, Q. et al also noticed that estradiol mediated ERK pathway via inhibiting MKP-1 expression, reducing the injury of axial flap by I/R (Jin et al 2017). Given these evidences, ERK pathway related molecules, especially MKP-1, might be involved in the mechanism of D-allose in the protective effect of I/R in the skin flap.…”

“…Interestingly, ERK signal pathway was noticed to be associated with the development of I/R injury (Choi et al 2017;Jin et al 2017). Given these information, we intended to investigate the function of D-allose in skin flap of rat followed by the injury of I/R and whether ERK signal pathway was involved in.…”

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

“…The ERK antagonist PD98059 (MedChemExpress,0.3mg/kg) was diluted in DMSO and PBS and administered intraperitoneally (i.p.) daily [21]. Flu (Aladdin Reagent Shanghai) was solubilized in sterile distilled water and administered intraperitoneally (i.p.)…”

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

“…daily [21]. Flu (Aladdin Reagent Shanghai) was solubilized in sterile distilled water and administered intraperitoneally (i.p.)…”