Uncoupling Protein-2 Deficient Mice Are Not Protected Against Warm Ischemia/Reperfusion Injury of the Liver

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• 作者：Khoi Le Minh M.D.^&lowast ; ;   ; ^&dagger ; ;   ; ; Andreas Berger^&lowast ; ;   ; ² ; Christian Eipel Ph.D.^&lowast ; ; Angela Kuhla Ph.D.^&lowast ; ; Thomas Minor M.D.^&Dagger ; ; Judith Stegemann^&Dagger ; ; Brigitte Vollmar M.D.^&lowast ; ;   ; ^{brigitte.vollmar@med.uni-rostock.de}
• 关键词：ATP ; hepatic energy charge ; hepatic microcirculation ; interleukin-6 ; reactive oxygen species
• 刊名：Journal of Surgical Research
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：171
• 期：2
• 页码：742-748
• 全文大小：938 K

文摘

Background

Uncoupling protein-2 (UCP2) might play an important role in mediating ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative phosphorylation and in the proton leak-associated increase of reactive oxygen species (ROS) production. The aim of this study was to elucidate the role of UCP2 in hepatic I/R injury.

Materials and Methods

UCP2 wild type and UCP2 deficient mice were subjected to I/R of the left liver lobe. Sham-operated animals without I/R served as controls. Intravital fluorescence microscopy was used for assessing postischemic microcirculatory dysfunction. Indicators of hepatic inflammatory response, oxidative stress, and bioenergetic status as well as histomorphology were investigated.

Results

Under sham conditions UCP2 ??mice presented slightly but not significantly higher levels of hepatic ATP and energy charge than wild type mice. In addition, they exhibited higher systemic IL-6 levels and intrahepatic leukocyte adherence. After exposure to I/R, the extent of reperfusion injury did not differ between UCP2 +/+ and UCP2 ??mice, as indicated by a comparable loss of sinusoidal perfusion, hepatic ATP, and energy charge levels, as well as rise of transaminases and disintegration of liver structures. Intrahepatic leukocyte adherence and plasma IL-6 levels of postischemic UCP2 ??mice still exceeded those of UCP2 +/+ mice.

Conclusions

UCP2 appears to be of minor relevance for the manifestation and extent of postischemic reperfusion injury in nondiseased livers with the increased ATP availability being counteracted by the higher pro-inflammatory IL-6 levels in UCP2 deficient mice.