Effect and Mechanism of Hydrogen Sulfide on Septic Rats with Myocardial Injury

XU Chao, ZHAO Hong-yan

Abstract

To study the effects of hydrogen sulfide (H2S) on myocardial injury in sepsis rats, and to explore the possible mechanism of H2S on myocardial injury induced by sepsis. Methods Cecal ligation and puncture (CLP) method was used to establish sepsis rat model. SD rats were randomly divided into 6 groups:sham operation group, sham operation + exogenous H2S donor sodium thiohydride group, pseudosurgery +H2S synthase cthioether-ether lyase (cystathionine-γ-lyase, CSE) inhibitor propargylglycine (propargylglycine, PAG) group, CLP model group, CLP model +NaHS group, CLP model +PAG group, 24 rats in each group. Blood and myocardial specimens were collected from the subgroups of COP for 6 h, 12 h and 24 h, respectively. Serum myocardial calcitonin I (cTnI) level, TNF-α, IL-10 were detected, and the pathological changes were observed by HE staining of rat myocardial tissue. The expression of CSE mRNA in cardiomyocytes was detected by RT-PCR, Western blot assay was used to detect the expression of cardiac transcription factor NF-κB in rats. Results There was no statistically significant difference in each group and time point of sham operation groups. Compared to the sham 12 h, 24 h group, the concentration of cTnI in serum, and pathological scores of myocardial tissue increased gradually (P<0.05) in the CLP 12 h and 24 h group. Compared to the CLP 12 h, 24 h group, in the CLP + NaHS 12 h, 24 h group, the concentration of cTnI in serum, and pathological scores of myocardial tissue, the expression of NF-κB, the level of TNF-α decreased and the expression of CSE mRNA and the level of IL-10 increased (P<0.05); in the CLP + PAG 12 h, 24 h group, the concentration of cTnI in serum, and pathological scores of myocardial tissue, the expression of NF-κB, the level of TNF-α increased gradually (P<0.05); and the expression of CSE mRNA and the level of IL-10 increased (P<0.05). Conclusion H2S plays a protective role in sepsis-induced myocardial injury, and the possible mechanism of this protective effect maybe by inhibiting the expression of NF-κB, reducing the content of TNF-α and improving the content of IL-10 in myocardial tissue.

 

Keywords: Hydrogen sulfide, Myocardial injury, Inflammatory factors

 

Full Text:

PDF


References


ANGUS DC, LINDE-ZWIRBLE WT, LIDICKER J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med,2001 ,29(7) s 1303-1310.

ESPER AM, MARTIN OS. Extending international sepsis epidemiology: the impact of organ dysfunction. Crit Care, 2009,13( 1 ): 120 [2017-06-16]. https://doi.org/10.1186/ cc7704.

TURNER A, TSAMITROS M, BELLOMO R. Myocardial cell injury in septic shock. Crit Care Med, 1999,27(9); 1775- 1780.

Y-HASSAN S, SETTERGREN M, HENAREH L. Sepsis- induced myocardial depression and takotsubo syndome. Acute Card Care,2014,16(3): 102-109.

ANTONUCCI E, FI ACC A DOR I E, DONADELLO K, et al. Myocardial depression in sepsis; from pathogennsis to clinical manifestations and treatment. J Crit Care, 2014, 29 (4): 500-511.

KRISHNAGOPALAN S, KUMAR A, PARRILLO JE, et al. Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care,2002,8(5) :376-388.

LOWICKA E, BELTOWSKI J. H2S - the third gas of interest for pharmacologists. Pharmacol Rep,2007,59(1);4- 24.

SOWMYA S, SWATHI Y, YEO AL, et al. Hydrogen sulfide: regulatory role on blood pressure in hyperhomocysteinemia. Vascul Pharmacol, 2010, 53 ( 3/4 ): 138-143.

TAMIZHSELVI R, MOORE PK, BHATIA M. Inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury. Pancreas,2008,36(4);24-31.

WHITEMAN M, WIN YARD PG. Hydrogen sulfide and inflammation; the good, the bad, the ugly and the promising. Expert Rev Clin Pharmacol,2011,4( 1); 13-32.

CHEN X, XU W, WANG Y, et al. Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-jcB expression, decreasing TNF-a levels and increasing IL-10 levels. Exp Ther Med,2014 ,8(2) :464-470.

COLLIN M, ANUAR FB, MUREH O, et al. Inhibition of endogenous Hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmaeol,2005,146(4) : 498-505.

ANG SF, SIO SW, MOOCHHALA SM. et al. Hydrogen sulfide upregulates cyclooxygenase-2 and prostaglandin E metabolite in sepsis-evoked acute lung injury via transient receptor potential vanilloid type 1 channel activation. J Immunol ,2011,187(9): 78-87.

REZKALLA S, KLONER RA, KHATIB G, et al. Effect of metoprolol in acute coxsackievirus B3 murine myocarditis. J Am Coll Cardiol, 1988.12(2):412-414.

JEREMIAS A, GIBSON CM. Narrative review; alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med,2005,142 (9):786-791.

RUDIGER A, SINGER M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med.2007,35(6); 1599-1608.

TAVENER SA, KUBES P. Is there a role for cardiomyocyte Toll-like receptor 4 in endotoxemia Trends in Cardiovascular Medicine, Trends Cardiovasc Med.2005,15(5); 153-157.

JOHN J, WOODWARD DB. WANG Y. etal. Troponin-I as a prognosticator of mortality in severe sepsis patients. J Crit Care,2010,25(2):270-275.

MAIER J. Cardiac troponnin I and troponin T: are enzymes still relevant as relevant cardiac markers? Clin Chim Acta, 1997,257( 1):99-115.

KLOUCHE К, POMMET S, AMIGUES L, et al. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock; relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med,2014,29(4) :229-237.

ABRAHAM E. WUNDERINK R. SILVERMAN H. et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA, 1995, 2 73 (12):934-941.

MA X, CHANG W. ZHANG C, et al. Staphylococcal Panton-Valentine leukocid in induces pro-inflammatory cytokine production and nuclear factor-kappa Bactivation in neutrophils. PLoS One, 2012, 7 (4); 349-352 [2017-06-16]. https://doi. org/10. 1371/journal, pone. 0034970.

LIBBY P. NAHRENDORF M, SWIRSKI FK. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease. J Am Coll Cardiol,2016,67(9) ; 1091- 1103.

LIU F, LIU GJ. LIU N. et al. Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats. Exp Ther Med,2015,9 (3): 1068-1074.


Refbacks

  • There are currently no refbacks.