Miyamoto K, Hiroshiba N, Tsujikawa A, Ogura Y
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Invest Ophthalmol Vis Sci. 1998 Oct;39(11):2190-4.
Leukocytes have been reported to be less deformable and more activated in diabetes. It has also been suggested that they cause microvascular occlusions that may cause diabetic microangiopathy. This study was designed to evaluate in vivo leukocyte dynamics in the retinal microcirculation of diabetic rats.
Streptozotocin (STZ)-induced diabetic rats 4 weeks after diabetes induction and spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats with 6 weeks' duration of diabetes were used in this study. Leukocyte dynamics were observed with acridine orange digital fluorography, using a nuclear fluorescent dye of acridine orange and high-resolution images from a scanning laser ophthalmoscope.
There was no significant difference in capillary leukocyte velocity between the STZ-induced diabetic rats (1.27 +/- 0.12 mm/sec, mean +/- SD) and nondiabetic control subjects (1.38 +/- 0.07 mm/sec) or between OLETF rats (1.31 +/- 0.17 mm/sec) and the nondiabetic controls, Long-Evans Tokushima Otsuka (LETO) rats (1.29 +/- 0.11 mm/sec). In contrast, the density of leukocytes trapped in the retinal microcirculation was significantly elevated in the STZ-induced diabetic (2.5-fold; P < 0.01) and the OLETF rats (2-fold; P < 0.01) compared with leukocyte density in the control subjects.
Pharmacologically induced and spontaneously diabetic rats showed increased leukocyte entrapment in the living retina in the early stages of diabetes. In light of the damaging potential of leukocytes, accumulation of leukocytes in diabetic retinas from the preretinopathy stage could cause microvascular occlusions and dysfunction, in turn causing diabetic retinopathy.
据报道,糖尿病患者体内的白细胞变形能力下降且活化程度更高。也有观点认为,白细胞会导致微血管阻塞,进而引发糖尿病微血管病变。本研究旨在评估糖尿病大鼠视网膜微循环中白细胞的体内动态变化。
本研究使用了链脲佐菌素(STZ)诱导糖尿病4周后的大鼠,以及病程为6周的自发性糖尿病大冢长-艾氏-德岛肥胖(OLETF)大鼠。采用吖啶橙数字荧光造影术,利用吖啶橙这种核荧光染料和扫描激光检眼镜获取的高分辨率图像来观察白细胞动态变化。
STZ诱导的糖尿病大鼠(1.27±0.12毫米/秒,平均值±标准差)与非糖尿病对照大鼠(1.38±0.07毫米/秒)之间,以及OLETF大鼠(1.31±0.17毫米/秒)与非糖尿病对照大鼠大冢长-艾氏-德岛(LETO)大鼠(1.29±0.11毫米/秒)之间,毛细血管白细胞速度均无显著差异。相比之下,与对照大鼠的白细胞密度相比,STZ诱导的糖尿病大鼠(2.5倍;P<0.01)和OLETF大鼠(2倍;P<0.01)视网膜微循环中滞留的白细胞密度显著升高。
药物诱导糖尿病大鼠和自发性糖尿病大鼠在糖尿病早期均表现出活体视网膜中白细胞滞留增加。鉴于白细胞具有潜在的损伤作用,糖尿病视网膜从视网膜病变前期开始白细胞的积聚可能会导致微血管阻塞和功能障碍,进而引发糖尿病视网膜病变。