Necrostatin-1 protects against ischemia/reperfusion injury by inhibiting receptor-interacting protein 1 in a rat flap model

作者：Hao Liu, Mingzi Zhang, Xinhang Dong, Yifang Liu, Hao Yan, Youbin Wang · 发表于：Journal of Plastic Reconstructive & Aesthetic Surgery · 年份：2018 · DOI：10.1016/j.bjps.2018.10.019 · 被引用次数：26 · 研究领域：Cell death mechanisms and regulation、Reconstructive Surgery and Microvascular Techniques、Cardiac Ischemia and Reperfusion

INTRODUCTION: The failure of reconstructive surgeries remains a challenge for plastic surgeons. Ischemia reperfusion (I/R) injury is considered to be one of the major problems in flap surgery. Necroptosis is a recently discovered and caspase-3-independent programed necrosis. Necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. Reports indicate that Nec-1 provides protection in ischemic models, such as brain, kidney, and heart. The aim of this study is to investigate the influence of Nec-1 on the I/R process in rat abdominal skin flaps. METHODS: Twenty male Sprague-Dawley rats, weighing 280-320 g, were randomly divided into three groups. The extended epigastric skin flap (6 cm × 9 cm) of rats was used. Three hours of complete ischemia was performed using a clamp, and the clamp was then removed to reperfusion the flap. Twenty-four hours after the onset of the reperfusion, the rats were assessed for flap survival and perfusion analysis. One sample (1 cm × 1 cm) was taken for H&E, TUNEL, electron microscopy, IHC staining for RIP-1, and ELISA analysis for caspase-3 activity. RESULTS: Compared to the CTL group, the flap in the Nec-1 group showed a higher survival rate and better blood perfusion. In histological observation, skin flap in the Nec-1 group showed less inflammatory infiltration than the CTL group. The AI in the CTL group was higher than that in the Nec-1 group and showed typical morphological changes of apoptotic cells. In IHC study, RIP-1 expression was higher...