Nitric oxide is an essential mediator of the protective effects of remote ischaemic preconditioning in a mouse model of liver ischaemia reperfusion injury
Résumé
NO (Nitric oxide) may protect the liver from IR (ischaemia reperfusion) injury. RIPC (remote ischaemic preconditioning) also protects against liver IR injury. The molecular mediator(s) of RIPC are currently unknown. The aim of this study was to assess the role of NO in hindlimb RIPC-induced protection against liver IR injury. Mice were allocated to the following groups: Sham; RIPC: 6 cycles of 4x4 minutes ischaemia/reperfusion of hindlimb; IR: 40 minutes lobar (70%) hepatic ischaemia and 2-hours reperfusion; RIPC+IR: RIPC followed by IR group procedures; C-PTIO+RIPC+IR: C-PTIO (a direct NO scavenger) was administered followed by the RIPC+IR group procedure. Hepatic MBF (microcirculatory blood flow) was measured throughout the experiment. Circulating NOx (nitrite and nitrate) levels, plasma liver transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. NOx concentrations were significantly elevated (P < 0.05) in the RIPC and RIPC+IR groups. Compared to liver IR alone, RIPC+IR preserved hepatic MBF during liver reperfusion (P < 0.05). In contrast C-PTIO+RIPC+IR reduced MBF compared to RIPC+IR (P < 0.05). RIPC+IR reduced plasma transaminases (P < 0.05), histopathological, and ultrastructural features of injury compared to IR alone. The protective effects of RIPC+IR in reducing liver IR injury were abrogated in the group that received antecedent C-PTIO (C-PTIO+RIPC+IR). In conclusion, NO is an essential mediator of the protection afforded by hindlimb RIPC against liver IR injury. The mechanisms underlying this protection involve preservation of the sinusoidal structure and maintenance of blood flow through the hepatic microcirculation.
Domaines
Médecine humaine et pathologie
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