Changes in the density and localisation of endothelin receptors in the early stages of rat diabetic retinopathy and the effect of insulin treatment
Changes in the density and localisation of endothelin receptors in the early stages of rat diabetic retinopathy and the effect of insulin treatment
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DOI：
10.1007/s001250051375
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发表时间：
2000-06-01
期刊：
影响因子：
8.2
通讯作者：
Fernandez-Durango, R
中科院分区：
文献类型：
--
作者：
De Juan, JA;Moya, FJ;Fernandez-Durango, R
目的/假说。内皮素系统（ET系统）与糖尿病视网膜病变发病前的视网膜血流异常有关。本研究旨在探讨糖尿病早期大鼠视网膜内免疫反应性内皮素-1和内皮素受体的密度和定位变化，以及胰岛素治疗对这些变化的影响。在糖尿病诱导后15、45和90天处死未治疗的、胰岛素治疗的和年龄匹配的对照组大鼠。结合法测定神经视网膜膜内皮素受体的密度和比例。采用显微放射自显像法和免疫组化法分别分析内皮素受体和免疫反应性内皮素-1的定位。诱导糖尿病15天后，未经治疗的链脲佐菌素糖尿病大鼠的视网膜神经膜内皮素受体两种亚型的密度与年龄匹配的对照大鼠相比有统计学意义的降低。而在第90天，内皮素B型受体密度显著高于对照组，糖尿病视网膜最内层内皮素B型受体和免疫反应性内皮素-1信号均增加。与对照组相比，胰岛素治疗90 d后，视网膜神经膜和视网膜最内层的内皮素受体A型上调。这些结果表明，在早期糖尿病视网膜病变中，内皮素系统在视网膜的血管和神经元成分中都发生了改变。胰岛素治疗引起的内皮素受体A型上调提示胰岛素可能参与视网膜微血管病变。
Aims/hypothesis. The endothelin system (ET system) has been implicated in the retinal blood flow abnormalities that precede the onset of diabetic retinopathy. This study was undertaken to assess whether the density and localisation of both the immunoreactive endothelin-1 and endothelin receptors in rat retina change in the early stages of diabetes and the insulin treatment would affect those changes.Methods. Untreated streptozotocin-diabetic, insulin-treated streptozotocin-diabetic and age-matched control rats were killed 15, 45 and 90 days after the induction of diabetes. Binding assays were used to determine the density and proportion of endothelin receptors in neural retinal membranes. Localisation of endothelin receptors and immunoreactive endothelin-1 were analysed by microautoradiography and immunohistochemistry, respectively.Results. Fifteen days after the induction of diabetes, the neural retinal membranes of untreated streptozotocin-diabetic rats showed a statistically significant decrease in the density of both endothelin receptor subtypes when compared with age-matched control rats. At 90 days, however, the density of endothelin receptors type B was statistically significantly higher than that of control rats, and the innermost layers of the diabetic retina also showed an increase of both endothelin receptor type B receptor and immunoreactive endothelin-1 signal. Insulin treatment during 90 days up-regulated endothelin receptor type A in neural retinal membranes and in the innermost layers of the retina when compared with control retinas.Conclusion/interpretation. These results show that the endothelin system is altered in both vascular and neuronal components of the retina in early diabetic retinopathy. The up-regulation of endothelin receptor type A induced by insulin treatment suggests that insulin might be involved in retinal microangiopathy.