Li Jiafeng, Li Yifan, Wang Xuanwei, Xie Yamin, Lou Junsheng, Yang Yute, Jiang Shuai, Ye Meihan, Chen Huaizhi, Diao Weiyi, Xu Sanzhong
Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Service Quality Management, Sanmen People's Hospital, Taizhou, China.
Phytother Res. 2023 Sep;37(9):4059-4075. doi: 10.1002/ptr.7864. Epub 2023 May 7.
Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co-administration of Pino with adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up-regulates SIRT3 expression by activating the AMP-activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS-induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC-1α signaling pathway.
随意皮瓣移植是整形手术中最常见的皮肤移植技术。尽管技术有所进步，但远端皮瓣坏死的发生率仍超过3%，这限制了其在临床实践中的应用。目前治疗远端皮瓣坏死的方法仍然缺乏。白杨素（Pino）可以在多种疾病（如心血管疾病）中抑制活性氧（ROS）和细胞死亡，但Pino在随意皮瓣中的作用尚未得到探索。因此，我们通过大体观察、多普勒检查、免疫组织化学和蛋白质印迹法，探究Pino如何提高皮瓣存活率及其具体的上游机制。结果表明，Pino可通过抑制ROS、焦亡和凋亡来提高随意皮瓣的活力。Pino与腺相关病毒沉默信息调节因子2同源物3（SIRT3）短发夹RNA共同给药可逆转上述效应，证明Pino对皮瓣的有益作用依赖于SIRT3。此外，我们还发现Pino通过激活AMP激活的蛋白激酶（AMPK）途径上调SIRT3表达。本研究证明，Pino可通过消除ROS以及由AMPK/PGC-1α信号通路触发的、通过激活SIRT3诱导的细胞死亡来提高随意皮瓣的活力。
