Lateef Humaira, Abatan Omorodola I, Aslam Muhammad Nadeem, Stevens Martin J, Varani James
Department of Pathology, University of Michigan, 1301 Catherine Road/Box 0602, Ann Arbor, MI 48109, USA.
Diabetes. 2005 Mar;54(3):855-61. doi: 10.2337/diabetes.54.3.855.
In the current study, rats were made diabetic with streptozotocin (STZ) and maintained for 8 weeks, during which time they were treated topically on alternative days with a solution of 0.1% all-trans retinoic acid in a vehicle of 70:30% ethanol/propylene glycol. STZ-induced diabetic rats treated with vehicle served as controls. Additional nondiabetic rats were treated with all-trans retinoic acid or vehicle in parallel. At the end of the 8-week period, rats from all four treatment groups were subjected to abrasion wound formation. Wounds healed more rapidly in vehicle-treated nondiabetic skin than in vehicle-treated diabetic skin (96% of the wound surface area closed in nondiabetic rats within 6 days vs. 41% closed in diabetic rats). Wounds in all-trans retinoic acid-treated diabetic skin healed more rapidly than wounds in vehicle-treated diabetic skin (85% of the wound surface area closed in all-trans retinoic acid-treated diabetic rats vs. 41% closed in vehicle-treated diabetic rats). At the histological level, recently healed skin from vehicle-treated diabetic rats was shown to contain a thin, wispy provisional matrix in which many of the embedded cells were rounded and some were pycnotic. In contrast, a much denser provisional matrix with large numbers of embedded spindle-shaped cells was observed in healed wounds from diabetic skin that had been pretreated with all-trans retinoic acid. The all-trans retinoic acid-treated diabetic skin was histologically similar to vehicle-treated (or all-trans retinoic acid-treated) skin from nondiabetic animals. In light of these findings, we suggest that prophylactic use of retinoid-containing preparations might be useful in preventing the development of nonhealing skin ulcers resultant from minor traumas in at-risk skin.
在本研究中，用链脲佐菌素（STZ）使大鼠患糖尿病，并维持8周，在此期间，每隔一天用0.1%全反式维甲酸溶于70:30%乙醇/丙二醇载体的溶液对其进行局部治疗。用载体治疗的STZ诱导糖尿病大鼠作为对照。另外，将非糖尿病大鼠平行用全反式维甲酸或载体进行治疗。在8周结束时，对来自所有四个治疗组的大鼠进行擦伤伤口形成处理。载体治疗的非糖尿病皮肤伤口比载体治疗的糖尿病皮肤伤口愈合更快（非糖尿病大鼠在6天内伤口表面积的96%闭合，而糖尿病大鼠为41%闭合）。全反式维甲酸治疗的糖尿病皮肤伤口比载体治疗的糖尿病皮肤伤口愈合更快（全反式维甲酸治疗的糖尿病大鼠伤口表面积的85%闭合，而载体治疗的糖尿病大鼠为41%闭合）。在组织学水平上，载体治疗的糖尿病大鼠新近愈合的皮肤显示含有薄而纤细的临时基质，其中许多嵌入的细胞呈圆形，有些细胞核固缩。相比之下，在全反式维甲酸预处理的糖尿病皮肤愈合伤口中观察到更致密的临时基质，有大量嵌入的梭形细胞。全反式维甲酸治疗的糖尿病皮肤在组织学上与非糖尿病动物的载体治疗（或全反式维甲酸治疗）皮肤相似。鉴于这些发现，我们建议预防性使用含维甲酸的制剂可能有助于预防高危皮肤因轻微创伤而导致的不愈合皮肤溃疡的发生。
