Huang Lijuan, Minematsu Takeo, Kitamura Aya, Quinetti Paes C, Nakagami Gojiro, Mugita Yuko, Oe Makoto, Noguchi Hiroshi, Mori Taketoshi, Sanada Hiromi
Departments of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan.
Department of Advanced Nursing Technology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan.
PLoS One. 2016 Jul 12;11(7):e0158647. doi: 10.1371/journal.pone.0158647. eCollection 2016.
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.
临床医生经常会遇到糖尿病患者上皮化延迟的情况，高血糖状态是其中一个原因。然而，伤口愈合延迟的潜在机制尚未完全阐明，且尚未确立有效促进高血糖患者上皮化的治疗方法。在此，我们提出一种新试剂——酰化高丝氨酸内酯（AHL），以改善高血糖大鼠因表皮基底膜形成紊乱导致的上皮化延迟。本实验通过注射链脲佐菌素诱导急性高血糖。在高血糖大鼠或对照大鼠的侧腹制造全层伤口。通过组间比较进行组织化学和免疫组织化学分析，以确定表皮再生中高血糖特异性异常。然后，我们研究了AHL对高血糖大鼠上皮化延迟的影响。组织学分析显示，高血糖大鼠的上皮化组织显著缩短（P < 0.05），基底膜结构异常（碎片化和不成熟），基底角质形成细胞增殖不足和过度增殖。用AHL处理伤口可减少基底膜异常，使增殖的表皮角质形成细胞分布正常，并显著促进高血糖大鼠的上皮化（P < 0.05），表明AHL对高血糖导致的异常上皮化具有改善作用。
