Panés J, Kurose I, Rodriguez-Vaca D, Anderson D C, Miyasaka M, Tso P, Granger D N
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Circulation. 1996 Jan 1;93(1):161-7. doi: 10.1161/01.cir.93.1.161.
Diabetes is associated with an increased incidence of ischemic organ damage. The objectives of present study were to compare the leukocyte-endothelial cell adhesive interactions and albumin leakage response of mesenteric venules to ischemia-reperfusion between control rats, rats with streptozotocin-induced diabetes, and rats with hyperglycemia induced by glucose infusion and to define the molecular determinants of the leukocyte accumulation elicited by ischemia-reperfusion in diabetic rats.
Under baseline conditions, lower venular shear rates and an increased number of rolling leukocytes were noted in diabetic rats, whereas the number of adherent and emigrated leukocytes did not differ from that in control rats. Spontaneous albumin leakage from mesenteric venules was markedly increased in diabetic rats but not in hyperglycemic nondiabetic rats. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration and albumin leakage in diabetic rats. Acute elevation of glucose levels did not modify the microvascular responses to ischemia-reperfusion compared with control rats. Antibodies directed against CD11/CD18, intercellular adhesion molecule-1 (ICAM-1), or P-selectin but not L-selectin significantly decreased the number of adherent and emigrated leukocytes after ischemia-reperfusion in diabetic rats. However, none of the antibodies significantly attenuated the increased albumin leakage response to ischemia-reperfusion in diabetic rats.
These results indicate that diabetes mellitus is associated with exaggerated leukocyte-endothelial cell adhesion and albumin leakage responses to ischemia-reperfusion. The enhanced leukocyte accumulation in response to ischemia-reperfusion is mediated by CD11/CD18-ICAM-1 interactions (firm adhesion) and P-selectin (rolling). The exaggerated albumin leakage response to ischemia-reperfusion in diabetics is not mediated by the recruited inflammatory cells.
糖尿病与缺血性器官损伤发生率增加相关。本研究的目的是比较对照大鼠、链脲佐菌素诱导的糖尿病大鼠以及葡萄糖输注诱导的高血糖大鼠肠系膜小静脉对缺血再灌注的白细胞 - 内皮细胞黏附相互作用和白蛋白渗漏反应，并确定糖尿病大鼠缺血再灌注引起的白细胞积聚的分子决定因素。
在基线条件下，糖尿病大鼠的小静脉剪切速率较低，滚动白细胞数量增加，而黏附及游出的白细胞数量与对照大鼠无差异。糖尿病大鼠肠系膜小静脉的自发性白蛋白渗漏明显增加，而高血糖非糖尿病大鼠则无此现象。缺血再灌注使糖尿病大鼠的白细胞黏附、游出及白蛋白渗漏显著增加。与对照大鼠相比，血糖水平的急性升高并未改变微血管对缺血再灌注的反应。针对CD11/CD18、细胞间黏附分子 -1（ICAM -1）或P - 选择素而非L - 选择素的抗体可显著减少糖尿病大鼠缺血再灌注后黏附及游出的白细胞数量。然而，这些抗体均未显著减弱糖尿病大鼠缺血再灌注后白蛋白渗漏增加的反应。
这些结果表明，糖尿病与对缺血再灌注的白细胞 - 内皮细胞黏附及白蛋白渗漏反应过度有关。对缺血再灌注的白细胞积聚增强是由CD11/CD18 - ICAM -1相互作用（牢固黏附）和P - 选择素（滚动）介导的。糖尿病患者对缺血再灌注的白蛋白渗漏反应过度并非由募集的炎症细胞介导。
