Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China; Chiese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China.
J Plast Reconstr Aesthet Surg. 2019 Feb;72(2):194-202. doi: 10.1016/j.bjps.2018.10.019. Epub 2018 Nov 19.
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.
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.
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 in the CTL group. But there was no significant difference between the two groups in caspase-3 activity detection.
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.
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）损伤被认为是皮瓣手术中的主要问题之一。坏死性凋亡是一种新发现的、不依赖于半胱天冬酶-3 的程序性细胞坏死。坏死抑制剂-1（Nec-1）是坏死性凋亡的特异性抑制剂。有报道称，Nec-1 可在脑、肾和心脏等缺血模型中提供保护。本研究旨在探讨 Nec-1 对大鼠腹部皮瓣 I/R 过程的影响。
20 只雄性 Sprague-Dawley 大鼠，体重 280-320g，随机分为三组。采用大鼠扩展上腹皮瓣（6cm×9cm）。用夹具夹闭 3 小时造成完全缺血，然后松开夹具再灌注皮瓣。再灌注 24 小时后，评估皮瓣存活和灌注情况。取 1 个样本（1cm×1cm）用于 H&E、TUNEL、电镜、RIP-1 的 IHC 染色和 caspase-3 活性的 ELISA 分析。
与 CTL 组相比，Nec-1 组的皮瓣存活率更高，血供更好。组织学观察显示，Nec-1 组皮瓣的炎症浸润较 CTL 组少。CTL 组的 AI 高于 Nec-1 组，且出现典型的凋亡细胞形态学改变。在 IHC 研究中，CTL 组的 RIP-1 表达较高，但两组间 caspase-3 活性检测无明显差异。
Nec-1 通过抑制 RIP-1 对皮瓣模型发挥 I/R 损伤保护作用；这使其成为临床有前途的新策略。
