Hammes H P, Strödter D, Weiss A, Bretzel R G, Federlin K, Brownlee M
Third Medical Department, Justus-Liebig-University, Giessen, Germany.
Diabetologia. 1995 Jun;38(6):656-60. doi: 10.1007/BF00401835.
Primary prevention with aminoguanidine-an inhibitor of advanced glycation end product (AGE) formation--has been successfully employed to prevent diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary intervention strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transplantation in the rat model. After 6 months of diabetes, one group was treated with aminoguanidine (50 mg/100 ml drinking water; D-AG) while another group received syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection (Tx). After an additional 4 months, both groups were compared to a normal (NC 10) and diabetic (DC 10) control group. Retinal autofluorescence was increased 2.5-fold after 6 months and increased 3.7-fold after 10 months of diabetes (p < 0.001). Aminoguanidine and islet Tx retarded the further accumulation of autofluorescence equally (p < 0.001 vs DC 10), although the values were higher than those observed in DC at 6 months (p < 0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries after 6 months and a 4.1-fold increase after 10 months. Treatment with aminoguanidine or islet Tx reduced but did not completely attenuate the progression of vascular occlusion (p < 0.001 vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01). Both treatments reduced endothelial proliferation (22.4% after 10 months; p < 0.001) and completely arrested pericyte dropout (40% after 10 months; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
氨基胍（一种晚期糖基化终末产物（AGE）形成抑制剂）的一级预防已成功用于预防大鼠糖尿病性视网膜病变。然而，在二级干预策略中抑制AGE形成是否仍然有效尚不清楚。本研究通过在大鼠模型中比较氨基胍二级干预与同基因胰岛移植来解决这个问题。糖尿病6个月后，一组用氨基胍治疗（50mg/100ml饮用水；D-AG），而另一组通过门静脉注射接受胶原酶-菲可分离胰岛的同基因移植（Tx）。再过4个月后，将两组与正常（NC 10）和糖尿病（DC 10）对照组进行比较。糖尿病6个月后视网膜自发荧光增加2.5倍，糖尿病10个月后增加3.7倍（p<0.001）。氨基胍和胰岛Tx同样延缓了自发荧光的进一步积累（与DC 10相比，p<0.001），尽管其值高于6个月时DC组观察到的值（p<0.001）。糖尿病与6个月后无细胞毛细血管增加2.7倍和10个月后增加4.1倍有关。用氨基胍或胰岛Tx治疗可减少但未完全减弱血管闭塞的进展（与DC 10相比，p<0.001；D-AG与DC 6相比，p<0.05；Tx与DC 6相比，p<0.01）。两种治疗均减少了内皮细胞增殖（10个月后为22.4%；p<0.001）并完全阻止了周细胞丢失（10个月后为40%；p<0.001）。（摘要截断于250字）
