Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia.
Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia.
复制标题
DOI：
--
复制
发表时间：
2000-11
影响因子：
4.4
通讯作者：
T. Kern;Jie Tang;Masakazu Mizutani;R. Kowluru;Ram H. Nagaraj;Giulio R. Romeo;Francesca Podesta
中科院分区：
文献类型：
--
作者：
T. Kern;Jie Tang;Masakazu Mizutani;R. Kowluru;Ram H. Nagaraj;Giulio R. Romeo;Francesca Podesta
目的探讨糖尿病视网膜病变早期视网膜毛细血管细胞凋亡与晚期组织学病变的关系，并比较氨基胍（AMG）对糖尿病和半乳糖喂养引起的视网膜病变的影响。方法四氧嘧啶诱导的糖尿病大鼠和30%半乳糖饲料喂养的大鼠（已知可诱导糖尿病样视网膜病变）被随机分配至含AMG（2.5g/kg饲料）或不含AMG的饲料。在糖尿病或半乳糖血症6至8个月后，制备视网膜胰蛋白酶抑制剂，并使用Tdt介导的dUTP缺口末端标记（TUNEL）反应结合核碎裂的形态学证据定量毛细血管细胞凋亡。在18个月的持续时间，周细胞血影和脱细胞毛细血管定量分离的血管。在研究4个月和研究18个月时，通过既定方法测量了几种晚期糖基化终产物（AGEs），以评估AMG的生化效应。结果与预期一样，糖尿病和半乳糖血症大鼠在6 ~ 8个月时TUNEL阳性毛细血管细胞的频率增加，在18个月时出现视网膜病变特征性血管病变。AMG对糖尿病大鼠早期细胞凋亡和晚期组织病理学改变均有抑制作用，但对半乳糖血症大鼠的这些异常均无抑制作用。与其对糖尿病大鼠视网膜病变的预防作用相反，AMG对血红蛋白AGE或尾胶原戊糖苷、荧光和热断裂时间的水平没有抑制作用。糖尿病4个月的持续时间并没有引起几个AGEs视网膜水平的可检测的增加。结论：视网膜微血管细胞早期凋亡的频率可以预测糖尿病和半乳糖血症视网膜病变的发生。AMG对糖尿病视网膜病变的有益作用是在半乳糖血症中不起作用或不太重要的途径上发挥的，并且可能与AGEs的积累无关。
PURPOSE To examine the relationship between early retinal capillary cell apoptosis and late histologic lesions of diabetic retinopathy and to compare the effects of aminoguanidine (AMG) on the retinopathies caused by diabetes and galactose feeding. METHODS Rats with alloxan-induced diabetes and rats fed a 30% galactose diet (known to induce diabetic-like retinopathy) were assigned randomly to receive diet with (2.5 g/kg diet) or without AMG. After 6 to 8 months of diabetes or galactosemia, retinal trypsin digests were prepared, and capillary cell apoptosis was quantitated using the Tdt-mediated dUTP nick-end labeling (TUNEL) reaction in association with morphologic evidence of nuclear fragmentation. At 18 months duration, pericyte ghosts and acellular capillaries were quantitated in the isolated vasculature. Several advanced glycation end products (AGEs) were measured at 4 months of study and at 18 months of study by established methods to assess biochemical effects of AMG. RESULTS As expected, both diabetic and galactosemic rats showed increased frequency of TUNEL-positive capillary cells at 6 to 8 months and vascular lesions characteristic of retinopathy at 18 months. AMG inhibited both the early apoptosis and late histopathology in the diabetic rats, but neither of these abnormalities in the galactosemic rats. In contrast to its preventative effect on retinopathy in the diabetic rats, AMG showed no inhibitory effect on levels of hemoglobin AGE, or tail collagen pentosidine, fluorescence, and thermal breaking time. Diabetes of 4 months' duration did not cause a detectable increase in retinal levels of several AGEs. CONCLUSIONS The frequency of early apoptosis in retinal microvascular cells predicted the development of the histologic lesions of retinopathy in diabetes as well as in galactosemia. The beneficial effect of AMG on retinal lesions in diabetes is exerted on pathways that are either not operative or are less important in galactosemia and that may not relate to the accumulation of AGEs.