Pharmacological inhibition of diabetic retinopathy - Aminoguanidine and aspirin
Pharmacological inhibition of diabetic retinopathy - Aminoguanidine and aspirin
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DOI：
10.2337/diabetes.50.7.1636
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发表时间：
2001-07-01
期刊：
影响因子：
7.7
通讯作者：
Engerman, RL
中科院分区：
文献类型：
--
作者：
Kern, TS;Engerman, RL
氨基胍和阿司匹林在糖尿病狗的EI年研究中对视网膜病变的发展的影响进行了研究。任何一种药物每天都以20-25 mg的剂量给予。Kg(-1)。天(-1)。由于高血糖的严重程度极大地影响视网膜病变的发展，因此特别致力于维持试验组和对照组的血糖水平相当。用胰酶消化法分离视网膜血管，光镜下观察视网膜病变。糖尿病5年后，如预期的那样，出现囊状毛细血管瘤、周细胞影、无细胞毛细血管、视网膜出血等病变。与糖尿病对照组相比，给予氨基胍基本上预防了视网膜病变，显著抑制了视网膜微动脉瘤、无细胞毛细血管和周细胞影的发展。在5年的研究中，阿司匹林显著抑制视网膜出血和无细胞毛细血管的发展，但对其他病变的影响较小。虽然糖尿病导致晚期糖基化终末产物(AGEs)水平显著升高(即尾胶原和主动脉中的戊糖苷，以及HB-AGE)，但氨基胍对这些糖基化参数没有显著影响，糖尿病患者视网膜蛋白的硝化显著增加，并被氨基胍抑制，但其抑制视网膜病变的生化机制尚不清楚。氨基胍(但不是阿司匹林)可以抑制糖尿病引起的尺神经传导速度的缺陷，但两种药物都没有发现对肾脏结构或蛋白排泄有影响。
Effects of aminoguanidine and aspirin on the development of retinopathy have been examined in Ei-year studies of diabetic dogs. Either agent was administered daily in doses of 20-25 mg . kg(-1) . day(-1). Because severity of hyperglycemia greatly influences development of the retinopathy, special effort was devoted to maintaining comparable glycemia in experimental and control groups. The retinal vasculature was isolated by the trypsin digest method, and retinopathy was assessed by Light microscopy, Diabetes for 5 years resulted, as expected, in saccular capillary aneurysms, pericyte ghosts, acellular capillaries, retinal hemorrhages, and other lesions. Administration of aminoguanidine essentially prevented the retinopathy, significantly inhibiting the development of retinal microaneurysms, acellular capillaries, and pericyte ghosts compared with diabetic controls. Aspirin significantly inhibited the development of retinal hemorrhages and acellular capillaries over the 5 years of study, but had less effect on other lesions. Although diabetes resulted in significantly increased levels of advanced glycation end products (AGEs) (namely, pentosidine in tail collagen and aorta, and Hb-AGE), aminoguanidine had no significant influence on these parameters of glycation, Nitration of a retinal protein was significantly increased in diabetes and inhibited by aminoguanidine, The biochemical mechanism by which aminoguanidine has inhibited retinopathy thus is not clear. Aminoguanidine (but not aspirin) inhibited a diabetes-induced defect in ulnar nerve conduction velocity, but neither agent was found to influence kidney structure or albumen excretion.