Grant M B, Ellis E A, Caballero S, Mames R N
Division of Endocrinology and Metabolism, College of Medicine, University of Florida, Gainesville 32610-0226, USA.
Exp Eye Res. 1996 Sep;63(3):233-44. doi: 10.1006/exer.1996.0112.
Plasminogen activator inhibitor-1 is secreted bidirectionally by endothelial cells, acts as the primary regulator of fibrinolysis and as a key modulator of extracellular matrix proteolysis. Elevated serum levels of plasminogen activator inhibitor-1 are observed in serum of diabetic individuals. We investigated whether plasminogen activator inhibitor-1 is overexpressed in capillaries of diabetic donors with non-proliferative retinopathy compared to non-diabetic donors. We also assessed plasminogen activator inhibitor-1 expression in an animal model of retinopathy induced by exposing rabbit retinas to insulin-like growth factor-I. Colloidal gold immunocytochemistry was used to quantify plasminogen activator-1 antigen in donor retinas from diabetic subjects (n = 10) and control subjects (n = 10). This technique was also used to examine expression of plasminogen activator inhibitor-1 for correlation with retinal changes in the insulin-like growth factor-I-induced retinopathy model (n = 14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects as compared to controls. In the rabbit model, the expression of plasminogen activator inhibitor-1 immunoreactivity correlated with pathological retinal changes. In both the diabetic human and insulin-like growth factor-I-injected rabbit, overproduction of plasminogen activator inhibitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular matrix surrounding these capillaries. Minimal plasminogen activator inhibitor-1 was detected in the retinas of non-diabetics and in control rabbits injected with either heat-inactivated insulin-like growth factor-I or balanced salt solution. These studies support the conclusion that plasminogen activator inhibitor-1 is overexpressed in the retinal capillaries of diabetics with non-proliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy.
纤溶酶原激活物抑制剂 -1 由内皮细胞双向分泌，是纤维蛋白溶解的主要调节因子，也是细胞外基质蛋白水解的关键调节因子。在糖尿病患者的血清中可观察到纤溶酶原激活物抑制剂 -1 的血清水平升高。我们研究了与非糖尿病供体相比，患有非增殖性视网膜病变的糖尿病供体的毛细血管中纤溶酶原激活物抑制剂 -1 是否过度表达。我们还评估了在将兔视网膜暴露于胰岛素样生长因子 -I 诱导的视网膜病变动物模型中纤溶酶原激活物抑制剂 -1 的表达。采用胶体金免疫细胞化学法对糖尿病受试者（n = 10）和对照受试者（n = 10）的供体视网膜中的纤溶酶原激活物 -1 抗原进行定量。该技术还用于检测胰岛素样生长因子 -I 诱导的视网膜病变模型（n = 14）中纤溶酶原激活物抑制剂 -1 的表达，以与视网膜变化进行相关性分析。与对照组相比，所有糖尿病受试者视网膜中的纤溶酶原激活物抑制剂 -1 免疫反应性均显著增加。在兔模型中，纤溶酶原激活物抑制剂 -1 免疫反应性的表达与视网膜病理变化相关。在糖尿病患者和注射胰岛素样生长因子 -I 的兔中，在毛细血管腔内、内皮细胞胞质内以及这些毛细血管周围的基底膜和细胞外基质中均可见纤溶酶原激活物抑制剂 -1 的过量产生。在非糖尿病患者的视网膜以及注射热灭活胰岛素样生长因子 -I 或平衡盐溶液的对照兔的视网膜中检测到极少量的纤溶酶原激活物抑制剂 -1。这些研究支持以下结论：在患有非增殖性糖尿病视网膜病变的糖尿病患者的视网膜毛细血管以及患有胰岛素样生长因子 -I 诱导的视网膜病变的兔的视网膜毛细血管中，纤溶酶原激活物抑制剂 -1 过度表达。
