Volume 9 , Issue 2 , December 2021 , Pages: 25 - 30
Ischemic Postconditioning Attenuates Ischemia/Reperfusion-induced Injury Through Activating Inflammatory Signaling Pathways
Tianyi Su, Department of Surgery, Nanan District People's Hospital, Chongqing, P. R. China
Tian Su, Department of Surgery, Chongqing Medical University, Chongqing, P. R. China
Received: Jul. 14, 2021;       Accepted: Jul. 27, 2021;       Published: Aug. 5, 2021
DOI: 10.11648/j.cb.20210902.12        View        Downloads  
The role of post-treatment in protecting organ ischemia and re-perfusion damage is increasingly recognized, however, its mechanism of the action is not very clear, all in all, it still needs further research. The purpose of this experiment is to investigate whether IPO can reduce I/R-induced liver damage through inhibiting inflammatory signaling pathways in rats. Rats were randomly divided into sham, I/R, IPO and LY294002+IPO groups. The levels of AST and ALT were assessed. The expression levels of IL-1, Akt, NF-κB-P65 and TNF-α were analyzed using western blot analysis. The expression levels of ALT, AST, IL -1, TNF-α and NF-κB-P65 were significant reduction in the IPO group compared with those in the I/R group. Furthermore, the protein expression level of phosphorylated Akt was observed to be significant increase in the livers of the rats in the IPO group compared with those in the I/R group. Moreover, LY294002 was found to offset the advantages of IPO. To the best of our knowledge, this study provided the clear evidence to show that IPO significantly reduced the injury caused by I/R, and it might protect the liver from hepatic injury through activating the phosphoinositide 3-kinase pathway, which increased the expression of Akt, and inhibited the protein expression of IL-1, NF-κB-P65 and TNF-α.
Ischemic Postconditioning, Inflammatory, Signaling Pathways
To cite this article
Tianyi Su, Tian Su, Ischemic Postconditioning Attenuates Ischemia/Reperfusion-induced Injury Through Activating Inflammatory Signaling Pathways, Cell Biology. Vol. 9, No. 2, 2021, pp. 25-30. doi: 10.11648/j.cb.20210902.12
Copyright © 2021 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
[ 1 ]
Brenner C, Galluzzi L, Kepp O and Kroemer G: Decoding cell death signals in liver inflammation. J Hepatol 59: 583-594, 2013.
[ 2 ]
Ngo BT, Beiras-Fernandez A, Hammer C and Thein E: Hyperacute rejection in the xenogenic transplanted rat liver is triggered by the complement system only in the presence of leukocytes and free radical species. Xenotransplantation 20: 177-187, 2013.
[ 3 ]
Ogawa K, Kondo T, Tamura T, Matsumura H, Fukunaga K, Oda T and Ohkohchi N: Influence of Kupffer cells and platelets on ischemia-reperfusion injury in mild steatotic liver. World J Gastroenterol 19: 1396-1404, 2013.
[ 4 ]
Llacuna L, Marí M, Lluis JM, García-Ruiz C, Fernández-Checa JC. and Morales A: Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion. Am J Pathol 174: 1776-1785, 2009.
[ 5 ]
Yamaguchi Y, Matsumura F, Liang J, et al: Neutrophil elastase and oxygen radicals enhance monocyte chemoattractant protein- expression after ischemia/reperfusion in rat liver. Transplantation 68: 1459-1468, 1999.
[ 6 ]
Bautista AP: Acute ethanol binge followed by withdrawal regulates production of reactive oxygen species andcytokine -induced neutrophil chemoattractant and liver injury during reperfusion after hepatic ischemia. Antioxid Redox Signal 4: 721-731, 2002.
[ 7 ]
Spencer NY, Zhou W, Li Q, et al: Hepatocytes produce TNF-α following hypoxia-reoxygenation and liver ischemia-reperfusion in a NADPH oxidase- and c-Src-dependent manner. Am J Physiol Gastrointest Liver Physiol 305: G84-G94, 2013.
[ 8 ]
Gong WH, Zheng WX, Wang J, Chen SH, Pang B, Hu XM and Cao XL: Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model. World J Gastroenterol 18: 4934-4943, 2012.
[ 9 ]
Elias- Miró M, Jiménez- Castro MB, Rodés J and Peralta C: Current knowledge on oxidative stress in hepatic ischemia/reper-fusion. Free Radic Res 47: 555-568, 2013.
[ 10 ]
Yang SL, Chen LJ, Kong Y, Xu D and Lou YJ: Sodium nitro- prusside regulates mRNA expressions of LTC4 synthesis enzymes in hepatic ischemia/reperfusion injury rats via NF-kappaB signaling pathway. Pharmacology 80: 11-20, 2007. 37 11. Bajt ML, Farhood A and Jaeschke H: Effects of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature. Am J Physiol Gastrointest Liver Physiol 281: G1188-G1195, 2001.
[ 11 ]
Zhai Y, Petrowsky H, Hong JC, Busuttil RW and Kupiec-Weglinski JW: Ischaemia- reperfusion injury in liver transplantation - from bench to bedside. Nat Rev Gastroenterol Hepatol 10: 79-89, 2013.
[ 12 ]
Zhang Q, Fu H, Zhang H, et al: Hydrogen sulfide preconditioning protects rat liver against ischemia/reperfusion injury by activating Akt-GSK-3β signaling and inhibiting mitochondrial permeability transition. PLoS One 8: e74422, 2013.
[ 13 ]
Yun N and Lee SM: Activation of protein kinase C delta reduces hepatocellular damage in ischemic preconditioned rat liver. J Surg Res 185: 869-876, 2013.
[ 14 ]
Song X, Zhang N, Xu H, Cao L and Zhang H: Combined preconditioning and postconditioning provides synergistic protection against liver ischemic reperfusion injury. Int J Biol Sci 8: 707-718, 2012.
[ 15 ]
Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA and Vinten-Johansen J: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285: H579-H588, 2003.
[ 16 ]
Huerta L, Rancan L, Simón C, et al: Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia /reperfusion in a swine lung autotransplant model. Eur J Cardiothorac Surg 43: 1194-1201, 2013.
[ 17 ]
Li J, Lai X, Chen Y, Niu B and Gong J: Endotoxin tolerance attenuates liver ischemia/reperfusion injury by down-regulation of interleukin-1 receptor-associated kinase 4 in kupffer cells. Transplant Proc 43: 2531-2535, 2011.
[ 18 ]
Sano T, Izuishi K, Hossain MA, et al: Hepatic preconditioning using lipopolysaccharide: association with specific negative regulators of the Toll-like receptor 4 signaling pathway. Transplantation 91: 1082-1089, 2011.
[ 19 ]
Elias-Miró M, Jiménez-Castro MB, Rodés J and Peralta C: Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res 47: 555-568, 2013.
[ 20 ]
Schriewer JM, Peek CB, Bass J and Schumacker PT: ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion. J Am Heart Assoc 2: e000159, 2013.
[ 21 ]
Sasaki M and Joh T: Oxidative stress and ischemia-reperfusion. injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr 40: 1-12, 2007.
[ 22 ]
Stewart RK, Dangi A, Huang C, et al: A novel mouse model of depletion of stellate cells clarifies their role in ischemia/reperfusion- and endotoxin-induced acute liver injury. J Hepatol 60: 298-305, 2014.
[ 23 ]
Watanabe T, Oowada S, Kobayashi HP, et al: The role of the new Ca2+ antagonist, CV159, in hepatic I/R injury-the evaluation of hepatic organ reducing activity using in vivo and ex vivo EPR. J Surg Res 145: 49-56, 2008.
[ 24 ]
Wang Y, Zhang ZZ, Wu Y, Ke JJ, He XH and Wang YL: Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway. Braz J Med Biol Res 46: 861-867, 2013.
[ 25 ]
Pignataro G, Esposito E, Sirabella R, Vinciguerra A, Cuomo O, Di Renzo G and Annunziato L: nNOS and p-ERK involvement in the neuroprotection exerted by remote postconditioning in rats subjected to transient middle cerebral artery occlusion. Neurobiol Dis 54: 105-114, 2013.
[ 26 ]
Vigneron F, Dos Santos P, Lemoine S, et al: GSK-3β at the crossroads in the signalling of heart preconditioning: implication of mTOR and Wnt pathways. Cardiovasc Res 90: 49-56, 2011.
[ 27 ]
Pagel PS, Krolikowski JG, Shim YH, et al: Noble gases without anesthetic properties protect myocardium against infarction by activating prosurvival signaling kinases and inhibiting mito- chondrial permeability transition in vivo. Anesth Analg 105: 562-9, 2007.
[ 28 ]
Klune JR and Tsung A: Molecular biology of liver ischemia/reper fusion injury: established mechanisms and recent advancements. Surg Clin North Am 90: 665-677, 2010.
[ 29 ]
Menger MD, Richter S, Yamauchi J and Vollmar B: Role of microcirculation in hepatic ischemia/reperfusion injury. Hepato gastroenterology 46 (Suppl 2): 1452-1457, 1999.
[ 30 ]
Shibuya H, Ohkohchi N, Tsukamoto S and Satomi S: Tumor necrosis factor-induced, superoxide-mediated neutrophil accu mulation in cold ischemic/reperfused rat liver. Hepatology 26: 113-120, 1997.
[ 31 ]
Shito M, Wakabayashi G, Ueda M, et al: Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat. Transplantation 63: 143-148, 1997.
Browse Journals by Subject