Transforming growth factor-beta and insulin-like growth factor-I in relation to diabetes-induced impairment of wound healing.
Transforming growth factor-beta and insulin-like growth factor-I in relation to diabetes-induced impairment of wound healing.
复制标题
转化生长因子-β 和胰岛素样生长因子-I 与糖尿病引起的伤口愈合受损有关。
DOI：
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发表时间：
1996
影响因子：
2.2
通讯作者：
Ziad N. Labbad
中科院分区：
文献类型：
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作者：
M. Bitar;Ziad N. Labbad
创面愈合受损是糖尿病的一种常见现象，但对其根本原因却知之甚少。本研究采用三种创伤模型：(I)线性皮肤切开(拉伸强度)，(Ii)皮下植入聚乙烯醇海绵PVAs(胶原沉积)，以及(Iii)不锈钢网状室(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)，研究了链脲佐菌素(STZ)诱导的糖尿病对愈合过程的影响。特异性IGF-I的放射免疫分析显示，糖尿病导致IGF-I水平下降42%(伤口液)和48%(血清)。免疫印迹发现，糖尿病患者伤口液中46 kDa IGF结合蛋白水平明显降低。一项基于增殖的生物测定表明，糖尿病伤口液中的转化生长因子-β水平也降低了(55%)。不同剂量的链脲佐菌素(25 mg-200 mg/kg)诱导的代谢严重程度不同的糖尿病创面抗张强度和PVAS胶原沉积呈进行性降低。相反，细胞外基质蛋白酶的酶谱分析显示，糖尿病伤口液中含有增加的21、69和72 kDa明胶酶水平。胶原蛋白载体中单剂量的转化生长因子-β(2微克)部分逆转了与糖尿病相关的标准化切口抗张强度的下降。这些数据支持这样的假设，即糖尿病的伤口愈合障碍至少部分是由于伤口环境中生长因子活性的不足所致。
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.