Harris A G, Skalak T C, Hatchell D L
Department of Biomedical Engineering, University of Virginia, Charlottesville 22908.
Int J Microcirc Clin Exp. 1994 May-Jun;14(3):159-66. doi: 10.1159/000178824.
Although diabetic retinopathy is a leading cause of blindness, the mechanisms underlying the disorder remain unresolved. Recent studies have reported both an increase in viscosity and a decrease in filterability of blood in diabetes, as well as increased activation of monocytes and granulocytes. These rheological effects have been implicated in capillary closure which is an early pathological change in diabetic retinopathy. The objective of this study was to quantitatively measure in vivo for the first time the resistance increase in capillary networks due to leukocyte-capillary plugging during experimental diabetes. Intravital measurements of plugging durations and frequencies were made throughout capillary networks in the spinotrapezius muscle of anesthetized rats subject to streptozotocin (STZ) induced hyperglycemia. These data were used to estimate the increase in microvascular flow resistance due to leukocyte plugging. The increase averaged 13.0% which is significantly different (p < 0.05) from the 1.1% observed in previous experiments with normal rats. Although the total white cell count was normal, the diabetic animals exhibited a significantly increased percentage of monocytes. A small but significant decrease in capillary diameter in the diabetic animals was also observed. Thus, leukocytes have a significant impact on microvascular hemodynamics in diabetic animals, and leukocyte-capillary plugging may be an important mechanism of capillary closure and subsequent microvascular dysfunction in diabetic retinopathy.
尽管糖尿病视网膜病变是导致失明的主要原因，但该疾病的潜在机制仍未得到解决。最近的研究报告称，糖尿病患者血液的粘度增加且滤过性降低，同时单核细胞和粒细胞的活化增加。这些流变学效应与毛细血管闭塞有关，而毛细血管闭塞是糖尿病视网膜病变的早期病理变化。本研究的目的是首次在体内定量测量实验性糖尿病期间白细胞 - 毛细血管堵塞导致的毛细血管网络阻力增加。在接受链脲佐菌素（STZ）诱导的高血糖的麻醉大鼠的斜方肌中，对整个毛细血管网络进行活体测量堵塞持续时间和频率。这些数据用于估计由于白细胞堵塞导致的微血管血流阻力增加。增加的平均值为13.0%，与之前对正常大鼠实验中观察到的1.1%有显著差异（p < 0.05）。尽管白细胞总数正常，但糖尿病动物的单核细胞百分比显著增加。还观察到糖尿病动物的毛细血管直径有小幅但显著的减小。因此，白细胞对糖尿病动物的微血管血流动力学有显著影响，白细胞 - 毛细血管堵塞可能是糖尿病视网膜病变中毛细血管闭塞及随后微血管功能障碍的重要机制。
