Transplantation proceedings · 2013
The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit model.
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Yang J, Sun H, Takacs P, Zhang Y, Liu J, Chang Y, Candiotti K A
Аннотация
BACKGROUND: Hepatic ischemic-reperfusion injury (HIRI) is a major cause of morbidity and mortality following liver surgery. Octreotide (Oct) has been reported to improve hepatocellular energy metabolism in a rat HIRI model. This study was designed to evaluate whether Oct could protect the liver of rabbits against ischemic-reperfusion (I/R) injury.
METHODS: Twenty-four adult New Zealand rabbits were randomly divided into a sham operated group (Control), an ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β) levels, and endotoxin (ETX) levels were measured during I/R.
RESULTS: Compared with the Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to the I/R group (P < .05). ALT, AST, LDH, IL-1β, and ETX levels were increased in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the increase was lower in the I/R + Oct group relative to the I/R group (P < .05). Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P < .05) and Bax expression in the I/R group was reduced compared with other groups (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than in the I/R group by microscopy.
CONCLUSIONS: Oct pretreatment attenuated hemodynamic changes and decreased liver enzyme changes induced by HIRI in a rabbit model. The protection mechanisms of Oct may be related to reduced ETX levels, down-regulation of the inflammatory cytokines TNFα and IL-1β, and inhibition of hepatocellular apoptosis, as well as the modulation of the mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears that Oct may be useful in decreasing liver injury after liver surgery and/or transplantation and may serve as a promising agent against HIRI.
METHODS: Twenty-four adult New Zealand rabbits were randomly divided into a sham operated group (Control), an ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β) levels, and endotoxin (ETX) levels were measured during I/R.
RESULTS: Compared with the Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to the I/R group (P < .05). ALT, AST, LDH, IL-1β, and ETX levels were increased in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the increase was lower in the I/R + Oct group relative to the I/R group (P < .05). Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P < .05) and Bax expression in the I/R group was reduced compared with other groups (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than in the I/R group by microscopy.
CONCLUSIONS: Oct pretreatment attenuated hemodynamic changes and decreased liver enzyme changes induced by HIRI in a rabbit model. The protection mechanisms of Oct may be related to reduced ETX levels, down-regulation of the inflammatory cytokines TNFα and IL-1β, and inhibition of hepatocellular apoptosis, as well as the modulation of the mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears that Oct may be useful in decreasing liver injury after liver surgery and/or transplantation and may serve as a promising agent against HIRI.
Предметные рубрики MeSH
AnimalsApoptosisArterial PressureBiomarkersCytokinesCytoprotectionDisease Models, AnimalEndotoxinsEnergy MetabolismEnzymesFemaleHeart RateInflammation MediatorsLiverLiver DiseasesMaleOctreotideProtective AgentsProto-Oncogene Proteins c-bcl-2RabbitsReperfusion InjuryTime Factorsbcl-2-Associated X Protein