Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats.
Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats.
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DOI：
10.1371/journal.pone.0158647
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sanada H
中科院分区：
文献类型：
--
作者：
Huang L;Minematsu T;Kitamura A;Quinetti PC;Nakagami G;Mugita Y;Oe M;Noguchi H;Mori T;Sanada H
临床医生经常遇到延迟上皮形成的糖尿病患者，其中一个原因是高葡萄糖条件。然而，延迟伤口闭合的潜在机制尚未完全阐明，并且尚未建立有效的治疗方法来增强高血糖患者的上皮形成。在这里，我们提出了一种新的试剂，酰化高丝氨酸内酯（阿勒），以改善延迟上皮形成由于在高血压大鼠的表皮基底膜的形成障碍。本实验采用链脲佐菌素诱发大鼠急性高脂血症。在高血糖或对照大鼠的侧腹上产生全层伤口。进行组织化学和免疫组化分析，以确定高血压特异性异常表皮再生组间比较。然后，我们研究了阿勒对高血压大鼠延迟上皮形成的影响。组织学分析显示，高脂血症大鼠上皮化组织明显缩短（P < 0.05），基底膜结构异常（断裂和不成熟），基底角朊细胞增殖低下或过度。阿勒可明显减轻高糖大鼠创面基底膜的异常改变，使增生的表皮角质形成细胞分布正常，并显著促进创面上皮化（P < 0.05），提示阿勒对高糖所致的创面上皮化异常有改善作用。
Clinicians often experience delayed epithelialization in diabetic patients, for which a high glucose condition is one of the causes. However, the mechanisms underlying delayed wound closure have not been fully elucidated, and effective treatments to enhance epithelialization in patients with hyperglycaemia have not been established. Here we propose a new reagent, acylated homoserine lactone (AHL), to improve the delayed epithelialization due to the disordered formation of a basement membrane of epidermis in hyperglycaemic rats. Acute hyperglycaemia was induced by streptozotocin injection in this experiment. Full thickness wounds were created on the flanks of hyperglycaemic or control rats. Histochemical and immunohistochemical analyses were performed to identify hyperglycaemia-specific abnormalities in epidermal regeneration by comparison between groups. We then examined the effects of AHL on delayed epithelialization in hyperglycaemic rats. Histological analysis showed the significantly shorter epithelializing tissue (P < 0.05), abnormal structure of basement membrane (fragmentation and immaturity), and hypo- and hyperproliferation of basal keratinocytes in hyperglycaemic rats. Treating the wound with AHL resulted in the decreased abnormalities of basement membrane, normal distribution of proliferating epidermal keratinocytes, and significantly promoted epithelialization (P < 0.05) in hyperglycemic rats, suggesting the improving effects of AHL on abnormal epithelialization due to hyperglycemia.