Bitar M S
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat.
Am J Pathol. 1998 Feb;152(2):547-54.
The aim of the present study was to examine corticosterone dynamics and its role in the pathogenesis of impaired wound healing in diabetes mellitus (DM). The streptozotocin-treated rat was used as an animal model for type I DM. A linear skin incision and subcutaneously implanted polyvinyl alcohol sponge disks were considered as wound-healing models. The data regarding corticosterone dynamics revealed diabetes-related increments in plasma corticosterone concentrations at various time intervals during the diurnal cycle (9:00 a.m., 12:00 noon, and 3:00 p.m.) Moreover, a reduction in the levels of hippocampal glucocorticoid receptors was also evident in this disease state. Immobilization-induced stress elevated plasma corticosterone levels in both control and 30-day diabetic rats. Although the diabetic rat seems capable of appropriately initiating a corticosterone stress response, it is dramatically impaired in its capacity to terminate it. A progressive decrease in collagen deposition on polyvinyl alcohol sponge and wounded skin tensile strength was seen as a function of the duration of diabetes. Similarly, polyvinyl alcohol sponges retrieved from 30-day diabetic rats also showed a marked reduction in the expression of mRNA transcripts for type I and type III collagen. A simulation of the impairment in wound-healing potential in DM was achieved by treating control animals with a supraphysiological dose of hydrocortisone. It is worthy of note that an endocrinological paradigm involving adrenalectomy and replacement therapy with hydrocortisone significantly improved the wound-related parameters, including collagen metabolism and wounded skin tensile strength in the streptozotocin diabetic rats. Overall, our data provide evidence that the diabetic state is associated with hypercortisolemia and that this phenomenon may contribute to impaired wound healing in DM.
本研究的目的是检测皮质酮动态变化及其在糖尿病（DM）伤口愈合受损发病机制中的作用。用链脲佐菌素处理的大鼠作为I型糖尿病的动物模型。线性皮肤切口和皮下植入聚乙烯醇海绵圆盘被视为伤口愈合模型。关于皮质酮动态变化的数据显示，在昼夜周期的不同时间间隔（上午9:00、中午12:00和下午3:00），糖尿病相关的血浆皮质酮浓度升高。此外，在这种疾病状态下，海马糖皮质激素受体水平也明显降低。固定诱导的应激使对照大鼠和糖尿病30天大鼠的血浆皮质酮水平均升高。虽然糖尿病大鼠似乎能够适当启动皮质酮应激反应，但其终止反应的能力却显著受损。随着糖尿病病程的延长，聚乙烯醇海绵上的胶原蛋白沉积和伤口皮肤抗张强度逐渐降低。同样，从糖尿病30天大鼠中取出的聚乙烯醇海绵也显示I型和III型胶原蛋白mRNA转录物的表达明显减少。通过用超生理剂量的氢化可的松处理对照动物，模拟了DM伤口愈合潜力的受损情况。值得注意的是，涉及肾上腺切除术和氢化可的松替代疗法的内分泌模式显著改善了链脲佐菌素糖尿病大鼠的伤口相关参数，包括胶原蛋白代谢和伤口皮肤抗张强度。总体而言，我们的数据表明糖尿病状态与高皮质醇血症有关，并且这种现象可能导致DM伤口愈合受损。
