DOI QR코드

DOI QR Code

Naloxone Postconditioning Alleviates Rat Myocardial Ischemia Reperfusion Injury by Inhibiting JNK Activity

  • Xia, Anzhou (Department of Pharmacology, Xuzhou Medical College) ;
  • Xue, Zhi (Department of Pharmacology, Xuzhou Medical College) ;
  • Wang, Wei (Department of Pharmacology, Xuzhou Medical College) ;
  • Zhang, Tan (Department of Pharmacology, Xuzhou Medical College) ;
  • Wei, Tiantian (Department of Pharmacology, Xuzhou Medical College) ;
  • Sha, Xingzhi (Department of Cardiology, The People's Hospital of Suining) ;
  • Ding, Yixun (Department of Cardiology, The People's Hospital of Suining) ;
  • Zhou, Weidong (Department of Cardiology, The People's Hospital of Suining)
  • Received : 2013.11.14
  • Accepted : 2014.01.06
  • Published : 2014.02.28

Abstract

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p<0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p<0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

Keywords

References

  1. Sekikawa A, Horiuchi BY, Edmundowicz D, Ueshima H, Curb JD, Sutton-Tyrrell K, Okamura T, Kadowaki T, Kashiwagi A, Mitsunami K, Murata K, Nakamura Y, Rodriguez BL, Kuller LH. A "natural experiment" in cardiovascular epidemiology in the early 21st century. Heart. 2003;89:255-257. https://doi.org/10.1136/heart.89.3.255
  2. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285:H579-588.
  3. Zhu M, Feng J, Lucchinetti E, Fischer G, Xu L, Pedrazzini T, Schaub MC, Zaugg M. Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res. 2006;72:152-162. https://doi.org/10.1016/j.cardiores.2006.06.027
  4. Zhang W, Miao Y, Zhou S, Jiang J, Luo Q, Qiu Y. Neuroprotective effects of ischemic postconditioning on global brain ischemia in rats through upregulation of hippocampal glutamine synthetase. J Clin Neurosci. 2011;18:685-689. https://doi.org/10.1016/j.jocn.2010.08.027
  5. Penna C, Pasqua T, Perrelli MG, Pagliaro P, Cerra MC, Angelone T. Postconditioning with glucagon like peptide-2 reduces ischemia/reperfusion injury in isolated rat hearts: role of survival kinases and mitochondrial KATP channels. Basic Res Cardiol. 2012;107:272. https://doi.org/10.1007/s00395-012-0272-6
  6. Glembotski CC, Thuerauf DJ, Huang C, Vekich JA, Gottlieb RA, Doroudgar S. Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion. J Biol Chem. 2012;287:25893-25904. https://doi.org/10.1074/jbc.M112.356345
  7. Chen S, Liu J, Liu X, Fu Y, Zhang M, Lin Q, Zhu J, Mai L, Shan Z, Yu X, Yang M, Lin S. Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes. J Ethnopharmacol. 2011;137:263-270. https://doi.org/10.1016/j.jep.2011.05.011
  8. Liu Y, Liao X, Xue FS, Xu YC, Xiong J, Yuan YJ, Wang Q, Liu JH, Zhao JX. Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats. Zhonghua Yi Xue Za Zhi. 2011;91:1493-1497.
  9. Mutoh J, Ohsawa M, Hisa H. Effect of naloxone on ischemic acute kidney injury in the mouse. Neuropharmacology. 2013; 71:10-18. https://doi.org/10.1016/j.neuropharm.2013.03.001
  10. Zhang T, Zhou WD, Xia AZ, Gu SL. Effect of p38 MAPK on naloxone alleviating myocardial ischemia reperfusion injury in rats. West China Journal of Pharmaceutical Sciences. 2011;26:460-462.
  11. Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994;94:1621-1628. https://doi.org/10.1172/JCI117504
  12. Ferrandi C, Ballerio R, Gaillard P, Giachetti C, Carboni S, Vitte PA, Gotteland JP, Cirillo R. Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats. Br J Pharmacol. 2004;142:953-960. https://doi.org/10.1038/sj.bjp.0705873
  13. Hori M, Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res. 2009;81:457-464.
  14. Jiang CM, Xu CQ, Mi Y, Li HZ, Wang R, Li WM. Calciumsensing receptor induced myocardial ischemia/reperfusion injury via the c-Jun NH2-terminal protein kinase pathway. Acta Cardiol Sin. 2010;26:102-110.
  15. Matsumoto N, Imamura R, Suda T. Caspase-8- and JNKdependent AP-1 activation is required for Fas ligand-induced IL-8 production. FEBS J. 2007;274:2376-2384. https://doi.org/10.1111/j.1742-4658.2007.05772.x
  16. Lee SE, Lim JW, Kim H. Activator protein-1 mediates docosahexaenoic acid-induced apoptosis of human gastric cancer cells. Ann N Y Acad Sci. 2009;1171:163-169. https://doi.org/10.1111/j.1749-6632.2009.04716.x
  17. Setoguchi D, Kakihana Y. Naloxone. Masui. 2013;62:5-9.
  18. Zhou P, Dong CL, Niu RX, Wu JX, Li YH. The effects of naloxone in free oxygen radical during myocardial ischemiareperfusion period. Journal of Medical Research. 2008;37:56-57.
  19. Qin YH, Shen H, Yang YS, Wen TB, Li TD. Naloxone inhibits generation of IL-8 and TXA2 from Ischemic and reperfused myocardium. Pharmaceutical J Chin People's Liberation Army. 2008;24:23-25.
  20. Wong GT, Li R, Jiang LL, Irwin MG. Remifentanil postconditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation. Acta Anaesthesiol Scand. 2010;54:510-518. https://doi.org/10.1111/j.1399-6576.2009.02145.x
  21. Zhang Y, Irwin MG, Wong TM. Remifentanil preconditioning protects against ischemic injury in the intact rat heart. Anesthesiology. 2004;101:918-923. https://doi.org/10.1097/00000542-200410000-00017
  22. Weber TP, Raufbake C, Grosse Hartlage MA, Rolf N, Stypmann J, Van Aken H, Berendes E, Meissner A. Naloxone prevents increased atrial natriuretic peptide release during regional myocardial ischaemia and stunning in awake dogs. Br J Anaesth. 2002;88:87-93. https://doi.org/10.1093/bja/88.1.87

Cited by

  1. Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury vol.2014, pp.None, 2014, https://doi.org/10.1155/2014/368376
  2. Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels vol.36, pp.6, 2015, https://doi.org/10.3892/ijmm.2015.2366
  3. Protective effect of sevoflurane on myocardial ischemia-reperfusion injury in rat hearts and its impact on HIF-1α and caspase-3 expression vol.14, pp.5, 2014, https://doi.org/10.3892/etm.2017.5078
  4. MicroRNA‐132 protects H9c2 cells against oxygen and glucose deprivation‐evoked injury by targeting FOXO3A vol.235, pp.1, 2020, https://doi.org/10.1002/jcp.28956