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

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)-α 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-α 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-α. 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-α, which also contributed to the lung-protective effect of sevoflurane.

Long‑term exposure to ethanol downregulates tight junction proteins through the protein kinase Cα signaling pathway in human cerebral microvascular endothelial cells

“…PKCα is a typical PKC isoform primarily expressed in vascular endothelial cells and the central nervous system ( 41 ). PKCα increases and decreases TJ permeability ( 21 ).…”

Mechanisms of lung ischemia-reperfusion injury

“…α1-antitrypsin [38*], anti-cytokine [11], or anti-HMGB1 [39] agents); 3) ventilation with gaseous molecules (e.g. carbon monoxide [40]) or inhaled anesthetic sevoflurane [41] that display anti-inflammatory properties; 4) growth factors (e.g. keratinocyte growth factor-2 [42]); 5) dietary supplements such as creatine [43]; and 6) cell-based therapies such as application of mesenchymal stem cells [44,45].…”

Protein kinase C isozyme expression in right ventricular hypertrophy induced by pulmonary hypertension in chronically hypoxic rats

“…Once activated, PKC can transmit signals to the nucleus via different signal transduction pathways. Acute stimulation of PKC has been reported to be associated with intracellular translocation ( 33 ). Chen et al ( 34 ) demonstrated that activation of nPKCδ increased the damage induced by ischemia and caused cardiac hypertrophy.…”