Diabetes exacerbates inflammatory responses to ischemia-reperfusion
Diabetes exacerbates inflammatory responses to ischemia-reperfusion
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DOI：
10.1161/01.cir.93.1.161
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发表时间：
1996-01-01
期刊：
影响因子：
37.8
通讯作者：
Granger, N
中科院分区：
文献类型：
--
作者：
Panes, J;Kurose, I;Granger, N
背景糖尿病与缺血性器官损伤的发生率增加有关。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和葡萄糖输注诱导的高血糖大鼠之间的白细胞-内皮细胞粘附相互作用和肠系膜微静脉对缺血-再灌注的白蛋白渗漏反应，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。在糖尿病大鼠中观察到较低的微静脉剪切率和增加的滚动白细胞数量，而粘附和迁移的白细胞数量与对照大鼠没有差异。糖尿病大鼠肠系膜微静脉自发性白蛋白渗漏显著增加，但在高血糖非糖尿病大鼠中无此现象。缺血再灌注引起糖尿病大鼠白细胞粘附和迁移以及白蛋白渗漏显著增加。与对照组大鼠相比，葡萄糖水平的急性升高并没有改变微血管对缺血再灌注的反应。抗CD 11/CD 18、细胞间粘附分子-1（ICAM-1）或P-选择素抗体可显著降低糖尿病大鼠缺血再灌注后粘附和迁移的白细胞数量，但对L-选择素无显著影响。然而，没有显着衰减的抗体增加白蛋白渗漏响应缺血-再灌注糖尿病rates.Conclusions这些结果表明，糖尿病与夸大白细胞-内皮细胞粘附和白蛋白渗漏响应缺血-再灌注。响应于缺血-再灌注的增强的白细胞积聚由CD 11/CD 18-ICAM-1相互作用（牢固粘附）和P-选择素（滚动）介导。糖尿病患者对缺血-再灌注的过度白蛋白渗漏反应不是由募集的炎性细胞介导的。
Background 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.Methods and Results 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.Conclusions 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.