Padilla Eugenia, Ganado Patricia, Sanz Mercedes, Zeini Miriam, Ruiz Emilio, Triviño Alberto, Ramírez Ana I, Salazar Juan J, Ramírez Jose M, Rojas Blanca, Hoz Rosa de, Tejerina Teresa
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Diabetes Metab Res Rev. 2005 Mar-Apr;21(2):132-42. doi: 10.1002/dmrr.487.
Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats.
Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections.
Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats.
We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats.
糖尿病视网膜病变(DR)是1型和2型糖尿病一种高度特异性的血管并发症。羟苯磺酸钙(DOBE)已被用于糖尿病视网膜病变的治疗试验,结果显示长期口服治疗后疾病进展减缓。本研究的目的是确定DOBE对链脲佐菌素(STZ)诱导的糖尿病大鼠血管及糖尿病视网膜病变的影响。
通过腹腔注射STZ(60mg/kg)诱导Wistar大鼠患糖尿病。大鼠被分为三组(n = 30)。第0组(G0):非糖尿病大鼠。第1组(G1):糖尿病发病后进行14个月的胰岛素治疗。第2组(G2):糖尿病发病后进行14个月的胰岛素治疗加DOBE(500mg/kg/天)。治疗结束时,检测血管反应性。在胰蛋白酶消化的视网膜整装片和视网膜切片上进行视网膜血管生成的研究。
糖尿病大鼠主动脉中乙酰胆碱诱导的舒张作用减弱,但在DOBE治疗组恢复到对照值(第0组、第1组和第2组分别为71.8±4.5%、53.3±0.5%、67.4±4.6%)。DOBE治疗还恢复了去甲肾上腺素(第0组、第1组和第2组分别为1.08±0.05μg、1.70±0.08μg、1.13±0.05μg)和咖啡因诱导的收缩作用。糖尿病状态未引起肠系膜动脉的任何改变。对视网膜消化物的分析显示,G1组存在血管迂曲、无细胞毛细血管、毛细血管局部聚集和周细胞数量减少。G2组观察到的血管变化似乎介于对照组和糖尿病大鼠之间。
我们表明,DOBE长期治疗可减轻链脲佐菌素诱导的糖尿病大鼠糖尿病视网膜病变的进展和血管反应性改变。