Bitar M S, Labbad Z N
Department of Pharmacology, Kuwait University, School of Medicine, Kuwait.
J Surg Res. 1996 Feb 15;61(1):113-9. doi: 10.1006/jsre.1996.0090.
Impaired wound healing is a well-documented phenomenon in diabetes mellitus, yet little is known of the fundamental cause of this pathology. This study examined the effects of streptozotocin (STZ)-induced diabetes on the healing process using three wound models: (i) a linear skin incision (tensile strength), (ii) subcutaneously implanted polyvinyl alcohol sponge PVAs (collagen deposition), and (iii) stainless steel mesh chamber (TGF-beta, IGF-I and its binding proteins, extracellular matrix remodeling enzymes). RIA specific for IGF-I revealed that diabetes induced a 42% (wound fluid) and a 48% (serum) reduction in IGF-I levels. IGF-II western ligand blots found that diabetes produced a marked reduction in the level of a wound fluid 46 kDa IGF binding proteins. A proliferation-based bioassay indicates that TGF-beta level is also reduced in diabetic wound fluid (55%). Diabetes of graded metabolic severity induced by variable doses of STZ (25 mg-200 mg/kg) showed stepwise reduction in wound tensile strength and PVAs collagen deposition. In contrast, zymographic analysis of extracellular matrix proteases revealed that the diabetic wound fluid contains increased levels of 21, 69, and 72 kDa gelatinases. A single dose of TGF-beta (2 micrograms) in a collagen vehicle partially reversed the diabetes-related decrease in the tensile strength of standardized incisions. These data support the premise that wound-healing impairment in diabetes is due, at least in part, to a deficiency in growth factor activity within the wound environment.
伤口愈合受损是糖尿病中一个有充分文献记载的现象，但对于这种病理状态的根本原因却知之甚少。本研究使用三种伤口模型，研究链脲佐菌素（STZ）诱导的糖尿病对愈合过程的影响：（i）线性皮肤切口（抗张强度），（ii）皮下植入聚乙烯醇海绵（PVA）（胶原沉积），以及（iii）不锈钢网室（转化生长因子-β、胰岛素样生长因子-I及其结合蛋白、细胞外基质重塑酶）。针对胰岛素样生长因子-I的放射免疫分析显示，糖尿病导致伤口液中胰岛素样生长因子-I水平降低42%，血清中降低48%。胰岛素样生长因子-II的western配体印迹发现，糖尿病导致伤口液中一种46 kDa胰岛素样生长因子结合蛋白的水平显著降低。基于增殖的生物测定表明，糖尿病伤口液中转化生长因子-β水平也降低（55%）。由不同剂量的链脲佐菌素（25 mg - 200 mg/kg）诱导的不同代谢严重程度的糖尿病，显示伤口抗张强度和聚乙烯醇海绵胶原沉积呈逐步降低。相反，细胞外基质蛋白酶的酶谱分析显示，糖尿病伤口液中21 kDa、69 kDa和七十二kDa明胶酶的水平升高。在胶原载体中单次注射转化生长因子-β（2微克）可部分逆转糖尿病相关的标准化切口抗张强度降低。这些数据支持这样一个前提，即糖尿病患者伤口愈合受损至少部分是由于伤口环境中生长因子活性不足所致。
