Generating and reversing chronic wounds in diabetic mice by manipulating wound redox parameters.
Generating and reversing chronic wounds in diabetic mice by manipulating wound redox parameters.
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DOI：
10.1155/2014/562625
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发表时间：
2014
影响因子：
4.3
通讯作者：
Martins-Green M
中科院分区：
文献类型：
--
作者：
Dhall S;Do DC;Garcia M;Kim J;Mirebrahim SH;Lyubovitsky J;Lonardi S;Nothnagel EA;Schiller N;Martins-Green M
到2025年，全世界将有5亿多人患有糖尿病; 1.25亿人将患上足部溃疡，2000万人将接受截肢手术，这将造成重大的健康问题。了解这些伤口是如何变成慢性的，将为扭转慢性提供见解。我们假设伤口中的氧化应激（OS）是慢性化产生的关键组成部分。我们使用愈合受损的db/db小鼠模型，并在损伤时抑制两种主要的抗氧化酶，过氧化氢酶和谷胱甘肽过氧化物酶，在伤口中产生高OS。这是必要的，足以触发伤口成为慢性。伤口最初含有多微生物群落，随着时间的推移，该群落被选择用于特定的生物膜形成细菌。为了逆转慢性化，我们用抗氧化剂α-生育酚和N-乙酰半胱氨酸治疗伤口，发现OS高度降低，生物膜对抗生素的敏感性增加，肉芽组织形成，胶原蛋白沉积和重塑。我们第一次展示了其中生物膜自发发展的慢性伤口的产生，说明了早期和持续的氧化还原失衡与伤口慢性发展中生物膜的存在相结合的重要性。该模型将有助于破译其他机制，并可能更好地诊断慢性和治疗人类慢性伤口。
By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress (OS) in wounds is a critical component for generation of chronicity. We used the db/db mouse model of impaired healing and inhibited, at time of injury, two major antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the wounds. This was necessary and sufficient to trigger wounds to become chronic. The wounds initially contained a polymicrobial community that with time selected for specific biofilm-forming bacteria. To reverse chronicity we treated the wounds with the antioxidants α-tocopherol and N-acetylcysteine and found that OS was highly reduced, biofilms had increased sensitivity to antibiotics, and granulation tissue was formed with proper collagen deposition and remodeling. We show for the first time generation of chronic wounds in which biofilm develops spontaneously, illustrating importance of early and continued redox imbalance coupled with the presence of biofilm in development of wound chronicity. This model will help decipher additional mechanisms and potentially better diagnosis of chronicity and treatment of human chronic wounds.
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DOI：
10.1073/pnas.1004204107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Grice, Elizabeth A.;Snitkin, Evan S.;Segre, Julia A.
通讯作者：
Segre, Julia A.
影响因子：
--
作者：
HEIM, WG;APPLEMAN, D;PYFROM, HT
通讯作者：
PYFROM, HT
影响因子：
2.9
作者：
Han, Anne;Zenilman, Jonathan M.;Lazarus, Gerald S.
通讯作者：
Lazarus, Gerald S.
影响因子：
9.4
作者：
Be, Nicholas A.;Allen, Jonathan E.;Jaing, Crystal J.
通讯作者：
Jaing, Crystal J.
影响因子：
--
作者：
Bonomo, SR;Davidson, JD;Mustoe, TA
通讯作者：
Mustoe, TA