Necrostatin-1 protects against ischemia/reperfusion injury by inhibiting receptor-interacting protein 1 in a rat flap model
Necrostatin-1 protects against ischemia/reperfusion injury by inhibiting receptor-interacting protein 1 in a rat flap model
复制标题
Necrostatin-1 通过抑制大鼠皮瓣模型中的受体相互作用蛋白 1 来防止缺血/再灌注损伤
DOI：
10.1016/j.bjps.2018.10.019
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发表时间：
2019-02-01
影响因子：
2.7
通讯作者：
Wang, Youbin
中科院分区：
文献类型：
--
作者：
Liu, Hao;Zhang, Mingzi;Wang, Youbin
简介：重建手术的失败仍然是整形外科医生面临的挑战。缺血再灌注（I / R）损伤是皮瓣外科面临的主要问题之一。坏死性凋亡是近年来发现的一种非caspase-3依赖的程序性坏死。Necrostatin-1（Nec-1）是坏死性凋亡的特异性抑制剂。报道表明，Nec-1在缺血模型中提供保护，例如脑、肾和心脏。方法：20只雄性SD大鼠，体重280- 320 g，随机分为3组，每组10只。采用大鼠上腹部扩大皮瓣（6cm × 9 cm）。使用夹钳进行三小时的完全缺血，然后移除夹钳以使皮瓣再灌注。再灌注开始后24小时，评估大鼠的皮瓣存活和灌注分析。结果：与CTL组相比，Nec-1组皮瓣成活率高，血流灌注好。组织学观察显示，Nec-1组皮瓣的炎症浸润比CTL组少。CTL组细胞凋亡率明显高于Nec-1组，呈典型的凋亡细胞形态学改变。免疫组化结果显示，RIP-1在CTL组中表达较高。结论：Nec-1通过抑制RIP-1对皮瓣I/R损伤具有保护作用，是一种有前景的新的治疗策略。(C)2018年英国整形，重建和美容外科医生协会。爱思唯尔有限公司出版
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 280-320g, were randomly divided into three groups. The extended epigastric skin flap (6 cm x 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 x 1 cm) was taken for HaE, 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 Al 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 in the CTL group. But there was no significant difference between the two groups in caspase-3 activity detection.Conclusion: Nec-1 has a protective effect against I/R injury through the inhibition of RIP-1 on the skin flap model; this makes it a promising novel strategy in clinical setting. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd.