Valproic acid enhances the viability of random pattern skin flaps: involvement of enhancing angiogenesis and inhibiting oxidative stress and apoptosis
Valproic acid enhances the viability of random pattern skin flaps: involvement of enhancing angiogenesis and inhibiting oxidative stress and apoptosis
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DOI：
10.2147/dddt.s186222
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Hongqiang Wu;Jian Ding;Lei Wang;Jinti Lin;Shihen Li;Guangheng Xiang;Liangfu Jiang;Huazi Xu;
中科院分区：
文献类型：
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作者：
Hongqiang Wu;Jian Ding;Lei Wang;Jinti Lin;Shihen Li;Guangheng Xiang;Liangfu Jiang;Huazi Xu;
研究背景随意皮瓣在整形外科中应用广泛，但皮瓣远端坏死限制了其临床应用。丙戊酸（VPA），一种组蛋白去乙酰化酶抑制剂和传统的抗癫痫药，可以促进皮瓣存活。材料与方法SD大鼠随机分为VPA组和对照组。建立改良McFarlane皮瓣模型后，腹腔注射VPA或生理盐水，每日1次，连续7 d。术后第7天检测皮瓣成活率、激光多普勒血流、含水量，行HE染色、免疫组化和Western blot分析，检测缺血皮瓣血管生成、细胞凋亡和氧化应激状态。结果术后第7天VPA可增加皮瓣成活面积、血流量和微血管数量，减轻水肿。VPA通过增强血管内皮生长因子（VEGF）mRNA转录和上调VEGF和钙粘蛋白5表达促进血管生成，通过减少caspase 3裂解抑制细胞凋亡，并通过增加超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平和降低丙二醛（MDA）水平缓解氧化应激。结论VPA可能通过促进血管生成、抑制氧化应激和细胞凋亡促进随意皮瓣成活。
Background Random skin flaps are commonly applied during plastic surgery, but distal flap necrosis limits their clinical applications. Valproic acid (VPA), a histone deacetylase inhibitor and a traditional antiepileptic agent, may promote flap survival. Materials and methods Sprague–Dawley rats were randomly divided into VPA-treated and control groups. All rats received VPA or saline by intraperitoneal injections once daily for 7 days after the modified McFarlane flap model was established. On postoperative day 7, flap survival, laser Doppler blood flow, and water content were examined for flap viability, hematoxylin and eosin staining (H&E), immunohistochemistry (IHC), and Western blot analysis, and the status of angiogenesis, apoptosis, and oxidative stress were detected in the ischemic flaps. Results VPA increased the survival area, blood flow, and number of microvessels in skin flaps on postoperative day 7 and reduced edema. VPA promoted angiogenesis by enhancing vascular endothelial growth factor (VEGF) mRNA transcription and upregulating VEGF and cadherin 5 expression, inhibited apoptosis via reduction of caspase 3 cleavage, and relieved oxidative stress by increasing superoxide dismutase (SOD) and glutathione (GSH) levels and reducing the malondialdehyde (MDA) level. Conclusion VPA promoted random skin flap survival by enhancing angiogenesis and inhibiting oxidative stress and apoptosis.