Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2018.07.001
Brazilian Journal of Anesthesiology
Scientific Article

Effects of propofol pretreatment on myocardial cell apoptosis and SERCA2 expression in rats with hepatic ischemia/reperfusion

Efeitos do pré-tratamento com propofol sobre a apoptose de células miocárdicas e expressão de SERCA2 em ratos com isquemia/reperfusão hepática

Shuzhen Yu; Yongqing Guo; Weiwei Zhang; Lina Zheng; Junming Ren; Jianmin Jin; Baofeng Yu; Yu Zhang; Hao Wang; Yuhong Zhang

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Abstract

Abstract Introduction: Hepatic ischemia-reperfusion injury is a common pathophysiological process in liver surgery. Whether Propofol can reduce myocardial ischemia-reperfusion injury induced by hepatic ischemia-reperfusion injury in rats, together with related mechanisms, still needs further studies. Objective: To investigate if propofol would protect the myocardial cells from apoptosis with hepatic ischemia-reperfusion injury. Methods: Male Sprague-Dawley rats (n = 18) were randomly allocated into three groups: Sham Group (Group S, n = 6), Hepatic Ischemia-reperfusion Injury Group (Group IR, n = 6) and Propofol Group (Group P, n = 6). Group S was only subjected to laparotomy. Group IR was attained by ischemia for 30 min and reperfusion for 4 h. Group P was subjected identical insult as in Group IR with the administration of propofol started 10 min before ischemia with 120 mg.kg−1, following by continuous infusion at 20 mg.kg−1.h−1. Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and cysteine-containing aspartic acid cleaved-caspase3 (cleaved-caspase3) were assayed by western blot and Altimeter polymerase chain reaction. Results: Apoptosis rate was increased, with mRNA and protein of SERCA2 down-regulated and cleaved-caspase3 up-regulated in Group IR compared with Group S (p < 0.01). Apoptosis rate was decreased, with mRNA and protein of SERCA2 up-regulated and cleaved-caspase3 down-regulated in Group P compared with Group IR (p < 0.01). Conclusions: Propofol can reduce hepatic ischemia-reperfusion injury-induced myocardial cell apoptosis, meanwhile, can up-regulate mRNA and protein of SERCA2 in rats.

Keywords

Propofol, Liver, Reperfusion injury, Myocardium, Endoplasmic reticulum Ca2+-ATPase2

Resumo

Resumo Introdução: A lesão hepática por isquemia-reperfusão é um processo fisiopatológico comum em cirurgias hepáticas. Mais estudos ainda são necessários para avaliar se o propofol pode reduzir a lesão de isquemia-reperfusão miocárdica induzida pela lesão de isquemia-reperfusão hepática em ratos, juntamente com os mecanismos que estão relacionados. Objetivo: Investigar se propofol protege as células do miocárdio da apoptose com a lesão hepática por isquemia-reperfusão. Métodos: Ratos machos da raça Sprague-Dawley (n = 18) foram alocados aleatoriamente em três grupos: Grupo Sham (Grupo S, n = 6), Grupo Lesão Hepática por Isquemia-reperfusão (Grupo IR, n = 6) e Grupo Propofol (Grupo P, n = 6). O Grupo S foi submetido apenas à laparotomia. O grupo IR foi submetido à isquemia por 30 min e reperfusão por 4 h. O grupo P foi submetido à mesma isquemia do grupo IR, com a administração de 120 mg.kg-1 de propofol iniciada 10min antes da isquemia, seguida de infusão contínua a 20 mg.kg-1.h-1. A apoptose celular foi examinada por meio do ensaio de marcação de terminações dUTP pela deoxinucleotidil transferase. Retículo endoplasmático Ca2+-ATPase2 (SERCA2) e caspase-3 do ácido aspártico contendo cisteína (caspase-3 clivada) foram avaliados com o ensaio western blot e reação em cadeia da polimerase. Resultados: A taxa de apoptose foi maior com mRNA e proteína de SERCA2 regulados para baixo e caspase-3 clivada suprarregulada no Grupo IR, em comparação com o Grupo S (p < 0,01). A taxa de apoptose foi menor com mRNA e proteína de SERCA2 suprarregulada e caspase-3 clivada sub-regulada no Grupo P, em comparação com o Grupo IR (p < 0,01). Conclusões: O propofol pode reduzir a apoptose de células miocárdicas induzida por lesão hepática por isquemia-reperfusão. Entretanto, pode suprarregular o mRNA e a proteína de SERCA2 em ratos.

Palavras-chave

Propofol, Fígado, Lesão de reperfusão, Miocárdio, Retículo endoplasmático Ca2+-ATPase2

References

Miranda LE, Capellini VK, Reis GS. Effects of partial liver ischemia followed by global liver reperfusion on the remote tissue expression of nitric oxide synthase: lungs and kidneys. Transplant Proc. 2010;42:1557-62.

Yang JC, Wang ZW, Li CL. Multiple organ injury at early stage of intestinal and hepatic ischemia-reperfusion in rats. J First Mil Med Univ. 2004;24:198-201.

Magan AA, Khalil AA, Ahmed MH. Terlipressin and hepatorenal syndrome: what is important for nephrologists and hepatologists. World J Gastroenterol. 2010;16:5139-47.

Cash WJ, McConville P, McDermott E. Current concepts in the assessment and treatment of hepatic encephalopathy. QJM. 2010;103:9-16.

Weinbroun AA, Hochhauser E, Rudick V. Multiple oxygen dysfunction after remote circulatory arrest; common pathway of radical oxygen species. J Trauma. 1999;47:691-8.

Omar MA, Wang L, Clanachan AS. Cardioprotection by GSK-3 inhibition: role of enhanced glycogen synthesis and attenuation of calcium overload. Cardiovasc Res. 2010;86:478-86.

Arii S, Teramoto K, Kawamura T. Current progress in the understanding of and therapeutic strategies for ischetmia and reperfusion injury of the liver. J Hepatobiliary Pancreat Surg. 2003;10:189-94.

Chen H, Lei ZL, Han SJ. Protective effects of propofol on renal injury during liver ischemia/reperfusion. Med J Chin PAPF. 2009;20:15-7.

Lotz C, Ping P, Kehl F. Letter by Lotz regarding article, "Reactive oxygen species-induced stimulation of 5′ AMP-activated protein kinase mediates sevoflurane-induced cardioprotection". Circulation. 2010;121:e399-400.

Kendzari DE, Tcheng JE. Double negatives. Am Heart J. 2003;145:9-11.

Goldhaber JI, Qayyum MS. Oxygen free radicals and excitation-contraction coupling. Antioxid Redox Signal. 2000;2:55-64.

Yoshiki U, Yoshiyuki A, Kosuke M. Endothelin-1 prolongs intracellular calcium transient decay in neonatal rat cardiac myocytes. Heart Vessels. 2012;27:98-105.

Sun GB, Sun H, Meng XB. Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats. Toxicol Appl Pharmacol. 2014;279:8-22.

Chang G, Zhang D, Liu J. Exenatide protects against hypoxia/reoxygenation-induced apoptosis by improving mitochondrial function in H9c2 cells. Exp Biol Med (Maywood). 2014;239:414-22.

Lu B, Zhao JL, Niu JC. Effect of propofol on myocardial injury induced by hepatic ischemla/reperfusion in rats and the role of PI3K/Akt signaling pathway. Chin J Anesthesiol. 2010;30:1250-3.

Gao WZ, Dan L, Tian ZD. Effects of propofol on lung injury and PI3K/Akt pathway in rats after liver ischemia and reperfusion. Chin J Pathol. 2013;29:488-92.

Jin YC, Kim W, Ha YM. Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo. Vascul Pharmacol. 2009;50:71-7.

Cheng YS, Chen Y, Li D. The mechanism and research status of calcium overload in myocardial ischemia/reperfusion injury. Chinese Med Innov. 2013;10:150-2.

Zhu N, Yao RL, Liu JS. The regulation of the apoptosis and oxidative stress of myocardial apoptosis and oxidative stress in rat limb ischemia/reperfusion. Chin J Gerontol. 2015;35:6666-8.

Talukder MA, Yang F, Nishijima Y. Reduced SERCA2a converts sub-lethal myocardial injury to infarction and affects postischemic functional recovery. J Mol Cell Cardiol. 2009;46:285-7.

Zhang MH, Yin YQ, He HY. Effects of dioscin on calcium channels in rat ventricular cardiomyocytes. Pharmacol Clin Chin Mater Med. 2011;27:23-6.

Talukder MA, Kalyanasundaram A, Zhao X. Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+ handling and decreases myocardial infarction. Am J Physiol Heart Circ Physiol. 2007;293:H2418-28.

Kim HS, Chang WC, Hwang KC. Effect of propofol on calcium homeostasis in hypoxia-reoxygenated neonatal rat cardiomyocytes. Eur J Pharmacol. 2008;594:139-45.

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