Effect and mechanism of recombinant human brain natriuretic peptide in alleviating myocardial ischemia-reperfusion injury by regulating mitogen activated protein kinase pathway_West China Medical Journal

Authors：

YANG Ming , LI Kunpeng ,  SONG Shutian , LI Guojing

Department of Cardiothoracic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P. R. China;

Corresponding author：

SONG Shutian, Email: shutian_song@163.com

Keywords：

Myocardial ischemia-reperfusion; recombinant human brain natriuretic peptide; mitogen activated protein kinase; inflammatory response; oxidative stress response

DOI：

10.7507/1002-0179.202109098

Video：

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Objective To study the effect and mechanism of recombinant human brain natriuretic peptide (rh-BNP) in alleviating myocardial ischemia-reperfusion (I/R) injury by regulating mitogen activated protein kinase (MAPK) pathway. Methods A total of 128 adult male Sprague-Dawley (SD) rats with specific pathogen free were selected. The SD rats were divided into groups according to random number table, including, sham operation (Sham) group, I/R group, I/R+rh-BNP group, negative control adenovirus (Ad-NC)+Sham group, Ad-NC+I/R group, Ad-NC+I/R+rh-BNP group, p38 mitogen-activated protein kinase adenovirus (Ad-p38MAPK)+I/R group and Ad-p38MAPK+I/R+rh-BNP group, with 16 SD rats in each group. Myocardial I/R injury model was established by ligation of left anterior descending coronary artery. Before modeling, rh-BNP was injected intraperitoneally or adenovirus was injected into myocardium; 180 minutes after reperfusion, the contents of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) in serum, myocardial infarction size, the contents of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and the expression of phosphorylated p38MAPK (p-p38MAPK), phosphorylated JNK (p-JNK) and phosphorylated extracellular regulated protein kinases 1/2 (p-ERK1/2) were detected. Results The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK and p-JNK in I/R group were higher than those in Sham group, p-ERK1/2 expression level was lower than that in Sham group (P<0.05). The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in I/R+rh-BNP group were lower than those in I/R group (P<0.05), the expression of p-JNK and p-ERK1/2 had no significant difference compared with I/R group (P>0.05). The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in Ad-p38mapk+I/R+rh-BNP group were higher than those in Ad-NC+I/R-rh-BNP group (P<0.05). Conclusion rh-BNP can alleviate myocardial I/R injury, which is related to inhibiting p38MAPK pathway, reducing inflammation response and oxidative stress response.

Citation： YANG Ming, LI Kunpeng, SONG Shutian, LI Guojing. Effect and mechanism of recombinant human brain natriuretic peptide in alleviating myocardial ischemia-reperfusion injury by regulating mitogen activated protein kinase pathway. West China Medical Journal, 2022, 37(10): 1538-1544. doi: 10.7507/1002-0179.202109098 Copy

1.	González-Montero J, Brito R, Gajardo AI, et al. Myocardial reperfusion injury and oxidative stress: therapeutic opportunities. World J Cardiol, 2018, 10(9): 74-86.
2.	Tibaut M, Mekis D, Petrovic D. Pathophysiology of myocardial infarction and acute management strategies. Cardiovasc Hematol Agents Med Chem, 2017, 14(3): 150-159.
3.	Li Y, Fei L, Wang J, et al. Inhibition of miR-217 protects against myocardial ischemia-reperfusion injury through inactivating NF-κB and MAPK pathways. Cardiovasc Eng Technol, 2020, 11(2): 219-227.
4.	Ren F, Mu N, Gao M, et al. Role of JNK signalling pathway and platelet-lymphocyte aggregates in myocardial ischemia-reperfusion injury and the cardioprotective effect of ischemic postconditioning in rats. Mol Med Rep, 2018, 18(6): 5237-5242.
5.	Su Z, Wei G, Wei L, et al. Effects of rhBNP on myocardial fibrosis after myocardial infarction in rats. Int J Clin Exp Pathol, 2015, 8(6): 6407-6415.
6.	Li KP, Zhang HY, Xu XD, et al. Recombinant human brain natriuretic peptide attenuates myocardial ischemia-reperfusion injury by inhibiting CD4⁺ T cell proliferation via PI3K/AKT/mTOR pathway activation. Cardiovasc Ther, 2020, 2020: 1389312.
7.	Li X, Peng H, Wu J, et al. Brain natriuretic peptide-regulated expression of inflammatory cytokines in lipopolysaccharide (LPS)-activated macrophages via NF-κB and mitogen activated protein kinase (MAPK) pathways. Med Sci Monit, 2018, 24: 3119-3126.
8.	Trojahn MM, Barilli SLS, Bernardes DDS, et al. B-type natriuretic peptide levels and diagnostic accuracy: excess fluid volume. Rev Gaucha Enferm, 2020, 41(spe): e20190095.
9.	Tiepolo A, Nougué H, Damoisel C, et al. Evolution of B-type natriuretic peptide and N-terminal pro-brain natriuretic peptide during acute decompensated heart failure in a chronic heart failure patient with reduced ejection fraction treated with Sacubitril/Valsartan: a case report. Eur Heart J Case Rep, 2019, 3(3): ytz108.
10.	Caprnda M, Zulli A, Shiwani HA, et al. The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure. Clin Exp Pharmacol Physiol, 2020, 47(7): 1120-1133.
11.	Peng Y, Wei H. Role of recombinant human brain natriuretic peptide combined with sodium nitroprusside in improving quality of life and cardiac function in patients with acute heart failure. Exp Ther Med, 2020, 20(1): 261-268.
12.	Takahashi N, Ogita M, Suwa S, et al. Prognostic impact of B-type natriuretic peptide on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction without creatine kinase elevation. Int Heart J, 2020, 61(5): 888-895.
13.	Shindo K, Fukuda H, Hitsumoto T, et al. Plasma BNP levels and diuretics use as predictors of cardiovascular events in patients with myocardial infarction and impaired glucose tolerance. Cardiovasc Drugs Ther, 2020, 34(1): 79-88.
14.	Ning C, Zheng Y, Li J, et al. Effects of recombinant human brain natriuretic peptide in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(11): e19479.
15.	Wang L, Xie L, Wei X, et al. Beneficial effects of early administration of recombinant human B-type natriuretic peptide in ST-elevation myocardial infarction patients receiving percutaneous coronary intervention treatment. Singapore Med J, 2019, 60(12): 621-625.
16.	Song Z, Zhao X, Liu M, et al. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway. Int J Exp Pathol, 2015, 96(6): 406-413.
17.	孙阿林, 张光芳, 肖丽, 等. 冻干重组人脑利钠肽对兔心肌梗死后心肌组织病理改变的影响及机制. 山东医药, 2016, 56(20): 31-33, 111.
18.	谭力力, 刘丽敏, 张秀春, 等. rh-BNP对大鼠心肌细胞H9c2缺氧/复氧损伤的保护作用及机制. 海南医学, 2018, 29(21): 2964-2967.
19.	Shvedova M, Anfinogenova Y, Atochina-Vasserman EN, et al. c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury. Front Pharmacol, 2018, 5(9): 715.
20.	Pei WN, Hu HJ, Liu F, et al. C-reactive protein aggravates myocardial ischemia/reperfusion injury through activation of extracellular-signal-regulated kinase 1/2. J Geriatr Cardiol, 2018, 15(7): 492-503.
21.	Ciocci Pardo A, González Arbeláez LF, Fantinelli JC, et al. Calcineurin/P38MAPK/HSP27-dependent pathways are involved in the attenuation of postischemic mitochondrial injury afforded by sodium bicarbonate co-transporter (NBCe1) inhibition. Biochem Pharmacol, 2019, 161: 26-36.

1. González-Montero J, Brito R, Gajardo AI, et al. Myocardial reperfusion injury and oxidative stress: therapeutic opportunities. World J Cardiol, 2018, 10(9): 74-86.
2. Tibaut M, Mekis D, Petrovic D. Pathophysiology of myocardial infarction and acute management strategies. Cardiovasc Hematol Agents Med Chem, 2017, 14(3): 150-159.
3. Li Y, Fei L, Wang J, et al. Inhibition of miR-217 protects against myocardial ischemia-reperfusion injury through inactivating NF-κB and MAPK pathways. Cardiovasc Eng Technol, 2020, 11(2): 219-227.
4. Ren F, Mu N, Gao M, et al. Role of JNK signalling pathway and platelet-lymphocyte aggregates in myocardial ischemia-reperfusion injury and the cardioprotective effect of ischemic postconditioning in rats. Mol Med Rep, 2018, 18(6): 5237-5242.
5. Su Z, Wei G, Wei L, et al. Effects of rhBNP on myocardial fibrosis after myocardial infarction in rats. Int J Clin Exp Pathol, 2015, 8(6): 6407-6415.
6. Li KP, Zhang HY, Xu XD, et al. Recombinant human brain natriuretic peptide attenuates myocardial ischemia-reperfusion injury by inhibiting CD4⁺ T cell proliferation via PI3K/AKT/mTOR pathway activation. Cardiovasc Ther, 2020, 2020: 1389312.
7. Li X, Peng H, Wu J, et al. Brain natriuretic peptide-regulated expression of inflammatory cytokines in lipopolysaccharide (LPS)-activated macrophages via NF-κB and mitogen activated protein kinase (MAPK) pathways. Med Sci Monit, 2018, 24: 3119-3126.
8. Trojahn MM, Barilli SLS, Bernardes DDS, et al. B-type natriuretic peptide levels and diagnostic accuracy: excess fluid volume. Rev Gaucha Enferm, 2020, 41(spe): e20190095.
9. Tiepolo A, Nougué H, Damoisel C, et al. Evolution of B-type natriuretic peptide and N-terminal pro-brain natriuretic peptide during acute decompensated heart failure in a chronic heart failure patient with reduced ejection fraction treated with Sacubitril/Valsartan: a case report. Eur Heart J Case Rep, 2019, 3(3): ytz108.
10. Caprnda M, Zulli A, Shiwani HA, et al. The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure. Clin Exp Pharmacol Physiol, 2020, 47(7): 1120-1133.
11. Peng Y, Wei H. Role of recombinant human brain natriuretic peptide combined with sodium nitroprusside in improving quality of life and cardiac function in patients with acute heart failure. Exp Ther Med, 2020, 20(1): 261-268.
12. Takahashi N, Ogita M, Suwa S, et al. Prognostic impact of B-type natriuretic peptide on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction without creatine kinase elevation. Int Heart J, 2020, 61(5): 888-895.
13. Shindo K, Fukuda H, Hitsumoto T, et al. Plasma BNP levels and diuretics use as predictors of cardiovascular events in patients with myocardial infarction and impaired glucose tolerance. Cardiovasc Drugs Ther, 2020, 34(1): 79-88.
14. Ning C, Zheng Y, Li J, et al. Effects of recombinant human brain natriuretic peptide in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(11): e19479.
15. Wang L, Xie L, Wei X, et al. Beneficial effects of early administration of recombinant human B-type natriuretic peptide in ST-elevation myocardial infarction patients receiving percutaneous coronary intervention treatment. Singapore Med J, 2019, 60(12): 621-625.
16. Song Z, Zhao X, Liu M, et al. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway. Int J Exp Pathol, 2015, 96(6): 406-413.
17. 孙阿林, 张光芳, 肖丽, 等. 冻干重组人脑利钠肽对兔心肌梗死后心肌组织病理改变的影响及机制. 山东医药, 2016, 56(20): 31-33, 111.
18. 谭力力, 刘丽敏, 张秀春, 等. rh-BNP对大鼠心肌细胞H9c2缺氧/复氧损伤的保护作用及机制. 海南医学, 2018, 29(21): 2964-2967.
19. Shvedova M, Anfinogenova Y, Atochina-Vasserman EN, et al. c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury. Front Pharmacol, 2018, 5(9): 715.
20. Pei WN, Hu HJ, Liu F, et al. C-reactive protein aggravates myocardial ischemia/reperfusion injury through activation of extracellular-signal-regulated kinase 1/2. J Geriatr Cardiol, 2018, 15(7): 492-503.
21. Ciocci Pardo A, González Arbeláez LF, Fantinelli JC, et al. Calcineurin/P38MAPK/HSP27-dependent pathways are involved in the attenuation of postischemic mitochondrial injury afforded by sodium bicarbonate co-transporter (NBCe1) inhibition. Biochem Pharmacol, 2019, 161: 26-36.

West China Medical Journal

Effect and mechanism of recombinant human brain natriuretic peptide in alleviating myocardial ischemia-reperfusion injury by regulating mitogen activated protein kinase pathway

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