Zhang Dupiao, Raza Mazhar Ali, Chen Jianpeng, Li Baolong, Liu Wenbin, Han Tao, Yan Hede, Jiang Liangfu
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325015, China.
Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou Medical University, Wenzhou 325088, China.
J Clin Med. 2023 Jan 19;12(3):809. doi: 10.3390/jcm12030809.
The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Fibroblast growth factor 9 (FGF9) was reported to exert a protective effect against myocardial damage and cerebral ischemia injury, but the impact of FGF9 in random flap survival is still unclear. In this study, we used a mouse model of random flaps to verify that FGF9 can directly increase flap survival area and blood flow intensity by promoting angiogenesis.
In total, 84 male C57BL/6 mice weighing between 22 and 25 g were randomly divided into three groups (n = 28 each group). After skin flap operation, one group served as a control, a treatment group received FGF9, and a treatment group received FGF9+U0126. All flap samples were incised on postoperative day 7.
Our results showed that flap survival was significantly increased in the FGF9 group compared with that in the control group. This protective function was restrained by U0126. The results of histopathology, laser Doppler, and fluorescent staining all showed significant increases in capillary count, collagen deposition, and angiogenesis. FGF9 also significantly increased the expression of antioxidant stress proteins SOD1, eNOS, HO-1, vascular marker proteins CD31, VE cadherin, and pericyte marker protein PDGFRβ. Western blot showed that the phosphorylation degree of ERK1/2 increased after FGF9 treatment, and the expression of Nrf2, a downstream factor, was u-regulated. Western blot and immunofluorescence results of apoptosis-related proteins cleaved caspase-3, BAX, and Bcl2 showed that FGF9 inhibited apoptosis. ERK inhibitor U01926 reduced the beneficial effects of FGF9 on skin flap survival, including promoting angiogenesis, and showing antiapoptosis and antioxidative stress activities.
Exogenous FGF9 stimulates angiogenesis of random flap and survival of tissue. the impact of FGF9 is closely linked to the prevention of oxidative stress mediated by ERK1/2-Nrf2. In the function of FGF9 in promoting effective angiogenesis, there may be a close interaction in the FGF9-FGFR-PDGFR-ERK-VE cadherin pathway. In particular, PDGFR and VE cadherin may interact.
由于坏死，随机皮瓣在整形外科重建中的应用受到限制。据报道，成纤维细胞生长因子9（FGF9）对心肌损伤和脑缺血损伤具有保护作用，但FGF9对随机皮瓣存活的影响仍不清楚。在本研究中，我们使用随机皮瓣小鼠模型来验证FGF9可通过促进血管生成直接增加皮瓣存活面积和血流强度。
总共84只体重在22至25克之间的雄性C57BL/6小鼠被随机分为三组（每组n = 28）。皮瓣手术后，一组作为对照组，一个治疗组接受FGF9，另一个治疗组接受FGF9 + U0126。所有皮瓣样本在术后第7天切开。
我们的结果表明，与对照组相比，FGF9组的皮瓣存活率显著提高。U0126抑制了这种保护作用。组织病理学、激光多普勒和荧光染色结果均显示毛细血管计数、胶原蛋白沉积和血管生成显著增加。FGF9还显著增加了抗氧化应激蛋白SOD1、eNOS、HO-1、血管标记蛋白CD31、VE钙黏蛋白和周细胞标记蛋白PDGFRβ的表达。蛋白质印迹法显示，FGF9处理后ERK1/2的磷酸化程度增加，下游因子Nrf2的表达上调。凋亡相关蛋白cleaved caspase-3、BAX和Bcl2的蛋白质印迹法和免疫荧光结果显示，FGF9抑制凋亡。ERK抑制剂U01926降低了FGF9对皮瓣存活的有益作用，包括促进血管生成以及显示抗凋亡和抗氧化应激活性。
外源性FGF9刺激随机皮瓣的血管生成和组织存活。FGF9的影响与预防由ERK1/2-Nrf2介导的氧化应激密切相关。在FGF9促进有效血管生成的功能中，FGF9-FGFR-PDGFR-ERK-VE钙黏蛋白途径中可能存在密切相互作用。特别是，PDGFR和VE钙黏蛋白可能相互作用。
