The involvement of c-Jun N-terminal kinase signaling pathway in the protective effect of estrogen on attenuating ischemia reperfusion injury in a rat flap model

Abstract

Objective To observe the protective effect of estrogen against ischemia reperfusion injury in axial flaps, and investigate the role of the c-Jun N-terminal kinase signaling pathway in estrogen′s protective effect. Methods An ischemia reperfusion injury model in the abdominal flap was created in 40 Wistar rats that were randomly divided into 4 groups: control (group A), ischemia reperfusion injury (group B), estrogen (group C) and JUN inhibitor (group D). Seven days postoperatively, gross observation of the flap, measurement of flap survival area and calculation of flap survival rate were carried out. The flap tissues were harvested for hematoxylin-eosin staining to observe histological changes, and for Western blot to quantify JNK, p-JNK and MKP-5 expression. The relationship between flap survival and JNK expression was analyzed. Results Flaps in groups C and D grew well. Flap survival rates in these two groups were significantly higher than that in group B, while pathological changes were milder. Expressions of JNK and p-JNK were significantly lower in flaps of groups C and D than in flaps of group B, while expression of JNK negative regulator MKP-5 was the opposite. Conclusion Estrogen can significantly improve the ischemia reperfusion injury in flaps and increase flap survival rate. The potential mechanism of estrogen′s protective effect can be through regulating Jun N-terminal kinase signaling pathway. Key words: Estrogens; Surgical flaps; Ischemia-reperfusion injury; c-Jun N-terminal kinase pathway