Fukunaga Yutaka, Izawa-Ishizawa Yuki, Horinouchi Yuya, Sairyo Eriko, Ikeda Yasumasa, Ishizawa Keisuke, Tsuchiya Koichiro, Abe Yoshiro, Hashimoto Ichiro, Tamaki Toshiaki
Department of Plastic and Reconstructive Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School.
Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
Wound Repair Regen. 2017 Apr;25(2):217-223. doi: 10.1111/wrr.12510. Epub 2017 Feb 13.
Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis.
随意型皮瓣可发生缺血性皮瓣坏死。缺血组织中会产生过量的活性氧并导致坏死。已证明硝基亚硝基吡啶（NO-NIF）具有强大的自由基清除能力。然而，尚未有关于NO-NIF对缺血性皮瓣坏死影响的研究。因此，他们在小鼠模型中评估了NO-NIF改善缺血性皮瓣坏死的潜力。在C57BL/6小鼠背部掀起一个1.0×3.0厘米的随意型皮瓣。术后立即通过局部注射给予NO-NIF，此后每24小时给药一次。在术后第7天评估皮瓣存活情况。在术后第1天和第3天采集皮瓣组织样本，以分析氧化应激、细胞凋亡和内皮功能障碍。与对照组（47.77±6.549%，p<0.01）相比，NO-NIF组皮瓣的存活面积显著增加（78.30±7.041%）。NO-NIF减轻了氧化应激、细胞凋亡和内皮功能障碍，这表现为丙二醛、p22phox蛋白表达、凋亡细胞数量、磷酸化p38 MAPK蛋白表达和血管细胞黏附分子-1蛋白表达降低，而内皮型一氧化氮合酶蛋白表达增加。总之，他们证明NO-NIF通过减轻氧化应激、细胞凋亡和内皮功能障碍来改善缺血性皮瓣坏死。NO-NIF被认为是治疗缺血性皮瓣坏死的候选药物。
