Ischemic preconditioning ameliorates microcirculatory disturbance through downregulation of TNF-alpha production in a rat cremaster muscle model.

摘要: Ischemia-reperfusion (I/R) injury is a complex process involving the generation and release of inflammatory cytokines, accumulation infiltration neutrophils macrophages, which disturbs microcirculatory hemodynamics. Nonetheless, ischemic preconditioning (IPC) known to produce immediate tolerance subsequent prolonged I/R insults, although its underlying mechanism largely remains unknown. Our study investigated role IκB-α-NF-κB-TNF-α (tumor necrosis factor-α) pathway in IPC's ability ameliorate I/R-induced disturbances rat cremaster muscle flaps. Male Sprague-Dawley rats were randomized (n=8 per group) into 3 groups: sham-operated control group, an group (4 h pudic epigastric artery ischemia followed by 2 reperfusion), IPC+I/R (3 cycles 10 min reperfusion before I/R). Intravital microscopy was used observe leukocyte/endothelial cell interactions quantify functional capillaries muscles. markedly increased number rolling, adhering, migrating leukocytes. It also observed that significantly TNF-α expression these injured tissues. On other hand, IPC prevented increases leukocyte adhesion, transmigration. Moreover, protein production mRNA downregulated group. Finally, IκB-α phosphorylation NF-κB (p65) nuclear translocation both suppressed IPC. These results indicated attenuated activation subsequently reduced expression, resulted amelioration I/R-injured