Exp Mol Med.  2015 Jun;47(6):e167. 10.1038/emm.2015.27.

Effects of sevoflurane on tight junction protein expression and PKC-alpha translocation after pulmonary ischemia-reperfusion injury

• Chai J
• Long B
• Liu X
• Li Y
• Han N
• Zhao P
• Chen W

• KMID: 2155421
• DOI: http://doi.org/10.1038/emm.2015.27

Abstract

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-alpha after ischemia-reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev-IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-alpha in the lung. Lung permeability was significantly increased after ischemia-reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-alpha. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-alpha, which also contributed to the lung-protective effect of sevoflurane.

MeSH Terms

Anesthetics, Inhalation/*therapeutic use
Animals
Capillary Permeability/drug effects
Gene Expression Regulation/drug effects
Lung/*drug effects/metabolism/pathology
Lung Diseases/*drug therapy/genetics/metabolism/pathology
Male
Methyl Ethers/*therapeutic use
Protein Kinase C-alpha/*metabolism
Protein Transport/drug effects
RNA, Messenger/genetics
Rats, Wistar
Reperfusion Injury/*drug therapy/genetics/metabolism/pathology
Zonula Occludens-1 Protein/analysis/*genetics
Anesthetics, Inhalation
Methyl Ethers
Protein Kinase C-alpha
RNA, Messenger
Zonula Occludens-1 Protein