Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes
Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes
复制标题
金雀异黄素通过抑制 1 型糖尿病中的超氧化物和 FoxO1/iNOS 通路来加速难治性伤口愈合
DOI：
10.1016/j.jnutbio.2012.02.011
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Li, Xuejun
中科院分区：
文献类型：
--
作者：
Tie, Lu;An, Yu;Li, Xuejun
糖尿病患者的难治性伤口是一种严重的并发症，通常导致截肢，治疗方案有限。本研究旨在确定大豆异黄酮对糖尿病伤口愈合的保护作用，并探讨其机制。链脲佐菌素（STZ）诱导的1型糖尿病小鼠与全层切除伤口接受0.2，1或5毫克/公斤/天的染料木黄酮通过皮下注射。染料木黄酮剂量依赖性地挽救糖尿病小鼠伤口闭合延迟。5 mg/kg/天剂量的染料木黄酮治疗显著增加了平均灌注率，并且在体外用染料木黄酮治疗可保护培养的内皮细胞免受高糖诱导的毛细血管形成损伤。糖尿病条件下显着增加超氧阴离子（O-2（中心点-））的生产和硝基酪氨酸的形成，并降低伤口组织中的亚硝酸盐水平。所有剂量的染料木黄酮治疗使升高的O-2（中心点-）产生和硝基酪氨酸形成正常化，并逆转了减弱的亚硝酸盐水平。在糖尿病伤口组织中，诱导型一氧化氮合酶（iNOS）被激活，染料木黄酮给药可防止iNOS活性增加。此外，染料木黄酮衰减糖尿病皮肤沉默信息调节因子1和叉头盒0转录因子1（FoxO 1）的水平和增强ac-FoxO 1的剂量依赖性的方式。染料木黄酮挽救了STZ诱导的1型糖尿病小鼠伤口愈合延迟和伤口血管生成改善，至少部分是通过抑制FoxO 1，iNOS活性和氧化应激。(C)2013 Elsevier Inc. All rights reserved.
Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens. The present study was designed to determine the protective effect of the soy isoflavone genistein on diabetic wound healing and investigate underlying mechanisms. Streptozotocin (STZ)-induced type 1 diabetic mice with full-thickness excisional wounds received 0.2, 1 or 5 mg/kg/day of genistein via subcutaneous injection. Genistein dose-dependently rescued the delay of wound closure in diabetic mice. A dose of 5 mg/kg/day of genistein treatment significantly increased the mean perfusion rate, and in vitro treatment with genistein protected against high glucose-induced impairment of capillary tube formation in cultured endothelial cells. Diabetic conditions significantly increased superoxide anion (O-2(center dot-)) production and nitrotyrosine formation, and decreased nitrite levels in wound tissues. Genistein treatment at all doses normalized the elevated O-2(center dot-) production and nitrotyrosine formation, and reversed the attenuated nitrite level. In diabetic wound tissues, the inducible nitric oxide synthase (iNOS) was activated, and genistein administration prevented increased iNOS activity. Moreover, genistein attenuated diabetic cutaneous silent information regulator 1 and forkhead box 0 transcription factor 1 (FoxO1) levels and potentiated ac-FoxO1 in a dose-dependent manner. Genistein rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetes in mice, at least in part, by suppression of FoxO1, iNOS activity and oxidative stress. (C) 2013 Elsevier Inc. All rights reserved.