Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.
Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.
复制标题
糖尿病缺血再灌注炎症反应增强的机制。
DOI：
10.1152/ajpheart.1998.275.5.h1773
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Piqué,JM
中科院分区：
文献类型：
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作者：
Salas,A;Panés,J;Elizalde,JI;Casadevall,M;Anderson,DC;Granger,DN;Piqué,JM
本研究的目的是评估脂质介质和粘附分子表达在糖尿病缺血再灌注诱导的炎症反应加重中的作用。通过活体显微镜研究了肠系膜微静脉中白细胞-内皮细胞相互作用。用双标记单克隆抗体技术检测内皮细胞间粘附分子（ICAM-1）的表达，用流式细胞术检测β2-整合素的表达。缺血再灌注引起糖尿病大鼠白细胞粘附和迁移的显着较大的增加，血小板活化因子（PAF）受体拮抗剂或白三烯合成抑制剂的预防。白三烯B4（LTB 4）灌流诱导类似的白细胞募集糖尿病和对照组大鼠，而PAF引起糖尿病大鼠更大的增加。CD 11 a，但不是CD 11b，在糖尿病动物的白细胞表达较高。糖尿病大鼠肠系膜和小肠内皮细胞ICAM-1表达与对照组无明显差异。这些结果表明，糖尿病与增强的缺血再灌注反应，这取决于PAF和白三烯。对PAF的敏感性增加，沿着CD 11 a表达增加，可能是糖尿病缺血再灌注炎症反应过度的原因。
The objective of the present study was to assess the role of lipid mediators and adhesion molecule expression in exacerbation of ischemia-reperfusion-induced inflammatory response in diabetes. Leukocyte-endothelial cell interactions were studied in mesenteric venules by intravital microscopy. Endothelial expression of intercellular adhesion molecule (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and β2-integrin expression was measured by flow cytometry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukotriene synthesis inhibitor. Leukotriene B4(LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PAF elicited larger increases in diabetic rats. CD11a, but not CD11b, expression was higher in leukocytes from diabetic animals. Endothelial ICAM-1 in mesentery and in intestine did not differ between diabetic and control rats. These results indicate that diabetes is associated with an enhanced response to ischemia-reperfusion that depends on both PAF and leukotrienes. An increased sensitivity to PAF, along with an increased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.