P物质对糖尿病鼠难愈创面修复的影响及其机制的初步研究

Effects and mechanism of substance P on the refractory cutaneous wounds of diabetic rats

目的研究外源性感觉神经肽P物质（substance P，SP）对糖尿病鼠难愈伤口的作用及其对创缘表皮干细胞（ESCs）迁移的影响。方法筛选糖尿病成模大鼠56只，随机分为对照组和SP组。于实验鼠背部制备2个直径1cm的全层皮肤切割伤口。SP组伤口给予外源性SP。分别于伤前及伤后4，7，10，14，17，21d描记伤口大小，动态观察各组治疗效果并取材，苏木精-伊红染色观察伤口上皮化速度和质量，并以角蛋白19（K19）、β1整合素做为ESCs表面标记物，观察创缘ESCs分布及数量变化规律。结果对照组和SP组创面伤后14d愈合率分别是83．94％和100％。组织学观察伤后SP组创面上皮化速度及愈合质量明显高于对照组。随着时间的推移，创缘标记阳性细胞数量明显增加，SP组较对照组增加明显，且主要位于新生基底层上层细胞及新生上皮。结论糖尿病难愈创面中，SP可以诱导ESCs向创缘迁移，这可能是SP加速创面愈合的原因之一。

Objective To investigate the effects of substance P（SP） on the refractory cutaneous wounds of diabetic rats and on the migration of epidermal stem cells （ESCs） around the wounds. Methods A total of 48 diabetic rats were randomly divided into two groups, ie, Group SP and control group. Two full-thickness wounds （ 1 cm in diameter each） were made on the back of each diabetic rats in Group SP. The wounds of Group SP were injected with SP. The wound areas were measured and biopsies were taken at days 4, 7, 10, 14, 17 and 21 after wound. The speed and quality of epithelialization were determined with hematoxylin and eosin staining. In the meantime, β1 integrin and keratin19 （K19） were employed to determine distribution of ESCs by using immunohistochemical method. Results The healing rate of wounds was 83.94 % in control group and 100% in Group SP at day 14 after wound. Histological examination showed that the speed and quality of epithelialization of Group SP were better than that in control group. Compared with control group, the positive cell number of β1 integrin and K19 in Group SP increased more significantly and were mainly located at upper stratum cells and epithelia of the basal lamina. Conclusion SP can induce more ESCs to migrate into the wound skin edge, as may be one of reasons for SP promoting wound healing.