Bui B V, Armitage J A, Tolcos M, Cooper M E, Vingrys A J
Department of Optometry and Vision Sciences, University of Melbourne, Victoria, 3010, Australia.
Diabetologia. 2003 Mar;46(3):401-8. doi: 10.1007/s00125-003-1042-7. Epub 2003 Mar 7.
We consider the nature of retinal dysfunction in streptozotocin rats and assess the functional benefits of administering an angiotensin enzyme inhibitor or an inhibitor of advanced glycation end product formation.
Sprague-Dawley rats (n=44) were randomly assigned to control (C=12, C(p)=4, C(a)=4) and diabetic groups (Streptozotocin, D=24). Diabetes was diagnosed based on a range of physiological and biochemical parameters at 4, 8 and 12 weeks. Streptozotocin animals were administered insulin daily (4 units protophane). Animals were treated with either an Angiotensin Converting Enzyme inhibitor (perindopril, C(p)=4, D(p)=8) or an inhibitor of advanced glycation end product formation (aminoguanidine, C(a)=4, D(a)=8). Dark-adapted electroretinograms were measured on anaesthetized animals at 12 weeks following streptozotocin treatment. Photoreceptoral and inner retinal responses were extracted, modelled and compared using ANOVA.
Streptozotocin injection increased blood glucose, glycosylated haemoglobin, fluid intake and urine volume, whereas body weight was decreased. Perindopril treatment produced improvements (p<0.05) in all indices, whereas aminoguanidine therapy produced some improvement in blood glucose and water intake. Streptozotocin rats showed losses of photoreceptoral-P3 (-27%), postreceptoral-P2 (-15%) and oscillatory potential (-19%) amplitudes of a similar magnitude. Perindopril therapy returned photoreceptoral and inner retinal function to within control limits. However, aminoguanidine treatment gave no significant functional improvement.
Our findings provide evidence for a selective neuropathy in diabetes with a primary photoreceptoral lesion. Treatment with perindopril, an angiotensin converting enzyme inhibitor, ameliorates the neuropathy.
我们研究链脲佐菌素诱导的大鼠视网膜功能障碍的本质，并评估给予血管紧张素酶抑制剂或晚期糖基化终产物形成抑制剂的功能益处。
将44只斯普拉格-道利大鼠随机分为对照组（C = 12只，C(p)=4只，C(a)=4只）和糖尿病组（链脲佐菌素诱导，D = 24只）。在第4、8和12周根据一系列生理和生化参数诊断糖尿病。链脲佐菌素诱导的动物每天给予胰岛素（4单位鱼精蛋白锌胰岛素）。动物分别接受血管紧张素转换酶抑制剂（培哚普利，C(p)=4只，D(p)=8只）或晚期糖基化终产物形成抑制剂（氨基胍，C(a)=4只，D(a)=8只）治疗。在链脲佐菌素治疗12周后，对麻醉的动物进行暗适应视网膜电图测量。提取、建模并使用方差分析比较光感受器和视网膜内层反应。
注射链脲佐菌素后血糖、糖化血红蛋白、液体摄入量和尿量增加，而体重下降。培哚普利治疗使所有指标均有改善（p<0.05），而氨基胍治疗使血糖和水摄入量有一定改善。链脲佐菌素诱导的大鼠光感受器P3波幅（-27%）、感受器后P2波幅（-15%）和振荡电位波幅（-19%）有相似程度的降低。培哚普利治疗使光感受器和视网膜内层功能恢复到对照范围内。然而，氨基胍治疗未产生显著的功能改善。
我们的研究结果为糖尿病中以原发性光感受器病变为主的选择性神经病变提供了证据。血管紧张素转换酶抑制剂培哚普利治疗可改善神经病变。
