Ischemic preconditioning improves liver tolerance to congestion-reperfusion injury in mice

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• 作者：Qiyi Zhang ; MD^a ; ^b ; ^c ; Sheng Yan ; MD^a ; ^b ; ^c ; Yang Tian ; MD^a ; ^b ; ^c ; Yuan Ding ; MD^a ; ^b ; ^c ; Jia Yao ; MD^a ; ^b ; ^c ; Hui Chen ; MD^a ; ^b ; ^c ; Zhiying Feng ; MD^a ; ^b ; ^c ; Kwabena Owusu-Ansah ; MD^a ; ^b ; ^c ; Shusen Zheng ; MD ; PhD^a ; ^b ; ^c ; ^{shusenzheng@zju.edu.cn" class="auth_mail}
• 关键词：Congestion ; Ischemic precondition ; Ischemia reperfusion injury ; Living donor liver transplantation
• 刊名：Journal of Surgical Research
• 出版年：1 June, 2014
• 年：2014
• 卷：189
• 期：1
• 页码：152-158
• 全文大小：1431 K

文摘

Background

Congestion-reperfusion injury (CRI) is a common complication after living donor liver transplantation, which has not been fully understood. It causes more severe inflammatory response as compared with ischemia-reperfusion injury (IRI). Ischemic preconditioning (IPC) has been endowed with powerful protective properties toward IRI. This study aimed to investigate whether IPC also has a protective effect against CRI and potential underlying mechanisms.

Materials and methods

Mice were randomly divided into sham operation, CRI, IPC-CRI, and congestion precondition (CPC-CRI) group. The hepatic vein of the left anterior hepatic lobe was occluded for 75聽min followed by reperfusion in the CRI group. The blood inflow was previously clamped for 10聽min followed by 10聽min of reperfusion just before occluding the hepatic vein in the IPC-CRI group. To imitating IPC in the CPC-CRI group, 10聽min of congestion followed by 10聽min of reperfusion just before CRI was performed. The animals were sacrificed at 2, 6, 24, 48聽h, and 7聽d after reperfusion. The blood and liver samples were collected for hepatic function assay, histology, terminal deoxynucleotidyl transferase dUTP nick end labeling, myeloperoxidase, and real-time polymerase chain reaction analysis.

Results

Mice in the CRI, IPC-CRI, and CPC-CRI group demonstrated elevated liver enzymes, histologic damage, cellular apoptosis, and inflammatory response compared with those in the sham operation group. Compared with the CRI group, mice in the IPC-CRI group expressed lower alanine transaminase activities (2聽h: 839.2聽卤聽132.5 versus 384.2聽卤聽94.8, P聽<聽0.01; and 6聽h: 680聽卤聽142.4 versus 342.3聽卤聽99.7, P聽<聽0.01) and lower myeloperoxidase levels (2聽h: 7.1聽卤聽4.0聽U/g versus 3.8聽卤聽1.6聽U/g, P聽<聽0.05; and 6聽h: 8.1聽卤聽1.3聽U/g versus 5.2聽卤聽3.0聽U/g, P聽<聽0.05). However, the alanine transaminase level in the CPC-CRI group was notably higher at 2聽h (839.2聽卤聽132.5 versus 1087.5聽卤聽192.5, P聽<聽0.05). Livers from mice in the IPC-CRI group聽showed better tissue integrity, diminished hepatocellular injury, and apoptosis at 2 and 6聽h. The messenger RNA transcriptions of interleukin 1 and interleukin 6 were significantly lower after 2-24聽h of reperfusion, whereas tumor necrosis factor 伪 and monocyte chemoattractant protein 1 were significantly lower after 24聽h of reperfusion in the IPC-CRI group.

Conclusions

IPC can significantly improve liver tolerance to CRI by attenuating neutrophil infiltration, proinflammatory cytokine formation, and hepatocytes apoptosis. This pretreatment strategy holds greater prospect of being translated into clinical use in living donor liver transplantation.