Nellore Kavitha, Harris Norman R
Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania, USA.
Microcirculation. 2004 Dec;11(8):645-54. doi: 10.1080/10739680490517668.
Vasoactive molecules can diffuse from venules to dilate closely paired arterioles and enhance capillary perfusion. Venular control of capillary flow has been found to be dependent on nitric oxide (NO), which might be scavenged rapidly in diabetic microvasculature due to the presence of activated leukocytes. This study attempts to improve venular control of capillary flow using fucoidan, which inhibits venular leukocvte adhesion.
Microvascular red blood cell velocity was measured in the mesentery of streptozotocin-induced diabetic rats, with and without fucoidan treatment, and in normal rats. Arteriolar pathways leading to branching capillaries were videotaped to measure the percent of the surrounding area occupied by a venule (% pairing). Microvascular wall NO was measured using fluorescent diaminofluorescein-2-diacetate in diabetic rats, with and without fucoidan treatment.
In normal rats, close pairing of venules to arterioles resulted in faster capillary flow. However, after 4-5 weeks of diabetes, the correlation between capillary velocity and % pairing was no longer significant. Capillary velocity and % pairing decreased approximately 50% in comparison to normal rats. Treatment of diabetic rats with fucoidan restored venular control of capillary flow and increased NO levels.
Leukocyte-derived mediators that scavenge NO may lead to inadequate venular control of capillary flow in diabetes.
血管活性分子可从小静脉扩散，使紧密配对的小动脉扩张并增强毛细血管灌注。已发现小静脉对毛细血管血流的控制依赖于一氧化氮（NO），而在糖尿病微血管中，由于活化白细胞的存在，NO可能会迅速被清除。本研究试图使用岩藻多糖来改善小静脉对毛细血管血流的控制，岩藻多糖可抑制小静脉白细胞黏附。
在链脲佐菌素诱导的糖尿病大鼠肠系膜中，测量有无岩藻多糖治疗时的微血管红细胞速度，并与正常大鼠进行比较。对通向分支毛细血管的小动脉路径进行录像，以测量小静脉占据周围区域的百分比（配对百分比）。使用荧光二氨基荧光素-2-二乙酸酯测量糖尿病大鼠在有无岩藻多糖治疗时的微血管壁NO。
在正常大鼠中，小静脉与小动脉的紧密配对导致毛细血管血流更快。然而，糖尿病4-5周后，毛细血管速度与配对百分比之间的相关性不再显著。与正常大鼠相比，毛细血管速度和配对百分比降低了约50%。用岩藻多糖治疗糖尿病大鼠可恢复小静脉对毛细血管血流的控制并提高NO水平。
清除NO的白细胞衍生介质可能导致糖尿病中小静脉对毛细血管血流的控制不足。
