Bitar M S, Farook T, Wahid S, Francis I M
Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, 13110 Safat, Kuwait.
J Surg Res. 1999 Apr;82(2):234-43. doi: 10.1006/jsre.1998.5541.
Failure of wounds to heal represents one of the major diabetic complications. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of impaired wound healing in diabetes mellitus.
The purpose of this study was to examine wound healing potential in diabetics under conditions in which the hypercortisolemic state is normalized.
Linear skin incision and polyvinyl alcohol (PVA) sponge were used as wound healing models. Six groups of rats matched with respect to age, sex, and strain were included in this study. Animals in groups 1 and 6 were injected with citrate buffer, whereas rats in groups 2,3,4, and 5 received streptozotocin (STZ, 55 mg/kg iv in citrate buffer). Five days later animals in groups 4,5, and 6 received insulin (group 4) and subcutaneous implantation of slow-releasing pellets containing either the GC receptor blocker RU 486 (group 5) or a high dose of GC (group 6).
Skin wound tensile strength and PVA sponge collagen metabolism were determined using tensiometric, spectrosphotometric, and polymerase chain reaction-based assays. In addition, cell infiltration and granulation tissue growth were assessed using a well-established histochemical technique.
Wound-related parameters including fibroplasia, neovascularization, and inflammatory cell numbers were reduced as a function of diabetes. Similarly, skin wound tensile strength, PVA sponge hydroxyproline content, and the levels of mRNA transcripts for type I and III collagen were also decreased in this disease state. This diabetes-related deficit in wound healing potential was ameliorated by subjecting diabetic animals to insulin treatment or by counteracting the excessive actions of GCs using both pharmacological (RU 486) and endocrinological (ADX) paradigms.
The current study supports the notion that GCs are implicated in the wound healing deficit of diabetics. Moreover, it illuminates the therapeutic potential of the GC receptor blocker (e. g., RU 486) in promoting wound repair under hypercortisolemic conditions including diabetes and Cushing's syndrome.
伤口愈合不良是糖尿病的主要并发症之一。新出现的证据表明糖皮质激素（GCs）参与了糖尿病伤口愈合受损的发病机制。
本研究的目的是在高皮质醇血症状态恢复正常的条件下，检测糖尿病患者的伤口愈合潜力。
采用线性皮肤切口和聚乙烯醇（PVA）海绵作为伤口愈合模型。本研究纳入了六组年龄、性别和品系匹配的大鼠。第1组和第6组动物注射柠檬酸盐缓冲液，而第2、3、4和5组大鼠接受链脲佐菌素（STZ，55mg/kg静脉注射于柠檬酸盐缓冲液中）。五天后，第4、5和6组动物接受胰岛素治疗（第4组），并皮下植入含有GC受体阻滞剂RU 486（第5组）或高剂量GC（第6组）的缓释微丸。
采用张力测定、分光光度法和基于聚合酶链反应的检测方法，测定皮肤伤口抗张强度和PVA海绵胶原代谢。此外，采用成熟的组织化学技术评估细胞浸润和肉芽组织生长。
与糖尿病相关的伤口相关参数，包括纤维组织增生、新血管形成和炎症细胞数量均减少。同样，在这种疾病状态下，皮肤伤口抗张强度、PVA海绵羟脯氨酸含量以及I型和III型胶原的mRNA转录水平也降低。通过对糖尿病动物进行胰岛素治疗，或使用药理学（RU 486）和内分泌学（肾上腺切除术）方法对抗GCs的过度作用，可改善这种与糖尿病相关的伤口愈合潜力缺陷。
本研究支持GCs与糖尿病患者伤口愈合缺陷有关的观点。此外，它还阐明了GC受体阻滞剂（如RU 486）在包括糖尿病和库欣综合征在内的高皮质醇血症条件下促进伤口修复的治疗潜力。
