Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia-reperfusion.

摘要: Leukocyte recruitment is a key feature in ischemia–reperfusion (I/R)-induced tissue injury. The aim of the present study was to investigate effect Rho-kinase inhibition on I/R-provoked leukocyte colon. C57BL/6 mice were subjected 30 min ischemia by clamping superior mesenteric artery followed 120 min reperfusion. Intraperitoneal pretreatment with selective inhibitors fasudil (4–40 mg/kg) and Y-27632 (1–10 mg/kg) administered prior induction colonic I/R. Leukocyte–endothelium interactions analyzed intravital fluorescence microscopy. Colonic content tumour necrosis factor-α (TNF-α) CXC chemokines macrophage inflammatory protein-2 (MIP-2) cytokine-induced neutrophil chemoattractant (KC) determined ELISA. Additionally, activity myeloperoxidase (MPO), marker infiltration, malondialdehyde (MDA), quantified. Fasudil decreased I/R-induced rolling adhesion 76% 96%, respectively. Moreover, interference reduced formation TNF-α, MIP-2 KC more than 68% reperfused reperfusion-provoked increase levels MPO MDA colon after 69% 42%, Our data demonstrate that decrease rolling, these findings show signalling regulates TNF-α chemokine as well lipid peroxidation Thus, targeting may be useful strategy order protect against pathological inflammation