Premium
Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning †
Author(s) -
Shinoda Masahiro,
Shimazu Motohide,
Wakabayashi Go,
Tanabe Minoru,
Hoshino Ken,
Kitajima Masaki
Publication year - 2002
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2002.02864.x
Subject(s) - medicine , ischemia , necrosis , tumor necrosis factor α , disturbance (geology) , tumor necrosis factor alpha , microcirculation , ischemic preconditioning , reperfusion injury , pathology , cardiology , biology , paleontology
Background:Brief periods of hepatic ischemia produce immediate tolerance for subsequent prolonged ischemia. Although the beneficial effect of this ischemic preconditioning is recognized, the mechanism itself remains poorly understood.Methods:Male Wistar rats were divided into two groups: a control group that was subjected to 30 min of ischemia + following reperfusion, and an ischemic preconditioning group that was subjected to 5 min of ischemia + 5 min of reperfusion + 30 min of ischemia + following reperfusion. By using this model, hepatic damage, microcirculatory disturbances, and tumor necrosis factor‐α protein production and mRNA expression were analyzed during the course of reperfusion in both groups. For the hepatic damage evaluations, hepatic enzyme levels, histology, apoptosis analysis, and intravital microfluorography for dead cells were examined. For the microcirculatory disturbance analysis, an adhesion molecule and intravital microfluorography for endothelial‐adherent leukocytes were examined.Results:In the ischemic preconditioning group, ischemia/reperfusion injuries (shown by hepatic enzymes elevation, histological degeneration, and increases in the number of apoptotic cells and microfluorographic dead cells) were markedly reduced. Moreover, microcirculatory disturbances represented by intercellular adhesion molecule‐1 expression and leukocyte adhesion on the endothelium were ameliorated. Tumor necrosis factor‐α protein production and mRNA expression were also suppressed in the ischemic preconditioning group.Conclusion:The suppression of tumor necrosis factor‐α and the subsequent amelioration of microcirculatory disturbances were observed, suggesting that the mechanism underlying the protective effect of ischemic preconditioning in hepatic ischemia/reperfusion injuries may involve tumor necrosis factor‐α and microcirculatory regulation. © 2002 Blackwell Publishing Asia Pty Ltd