Research Report
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2014; 20(28): 9506-9512
Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9506
Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion
Bergthor Björnsson, Anders Winbladh, Linda Bojmar, Tommy Sundqvist, Per Gullstrand, Per Sandström
Bergthor Björnsson, Anders Winbladh, Per Gullstrand, Per Sandström, Department of Surgery, County Council of Östergötland, 581 85 Linköping, Sweden
Bergthor Björnsson, Anders Winbladh, Linda Bojmar, Tommy Sundqvist, Per Gullstrand, Per Sandström, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 581 85 Linköping, Sweden
Author contributions: All authors participated in designing the research; Björnsson B, Winbladh A and Bojmar L performed the research; all authors contributed to the interpretation of the results and writing the paper.
Supported by Gösta Milton Donation Fund (Partly)
Correspondence to: Bergthor Björnsson, MD, Department of Surgery, County Council of Östergötland, 581 85 Linköping, Sweden. bergthor.bjornsson@lio.se
Telephone: +46-10-1030000 Fax: +46-10-1033570
Received: February 12, 2014
Revised: April 12, 2014
Accepted: May 23, 2014
Published online: July 28, 2014
Processing time: 164 Days and 9.7 Hours
Abstract

AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI).

METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed.

RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (ΔCt: 3.44 ± 0.57) group than in the IPC (ΔCt: 5.86 ± 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (ΔCt: 1.88 ± 0.53 to 4.81 ± 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 ± 2.2 to 4.7 ± 1.2 μmol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 ± 2.1 to 6.4 ± 1.5 μmol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups.

CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

Keywords: Ischemia-reperfusion injury; Preconditioning; Remote preconditioning; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; Inducible nitric oxide synthase; Interleukin-1 receptor

Core tip: Ischemic preconditioning has been shown to reduce ischemia/reperfusion injury (IRI) in the liver. NO has been shown to be important in the preconditioning process as well as in IRI. This study shows that ischemic preconditioning (IPC) but not remote ischemic preconditioning (R-IPC) reduces inducible nitric oxide synthase and interleukin 1 receptor transcription during early reperfusion. As it has been shown that IPC protects the liver more than R-IPC, this reduction in inflammatory activation may be important. In addition, this study shows that nitrite and nitrate are consumed in the liver during ischemia, unlike the levels in peripheral blood.