Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation

doi:10.5847/wjem.j.issn.1920-8642.2013.01.012

Abstract

Abstract:

BACKGROUND: This study was undertaken to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in rat cerebral cortex and the effects of β-sodium aescinate (SA) administration after return of spontaneous circulation (ROSC).
METHODS: Sixty rats were divided into three groups: SA group, injected intraperitoneally with SA instantly after ROSC; control group, injected intraperitoneally with normal saline; and sham-operated group, without cardiac arrest or SA. The cardiac arrest model was established using asphyxiation and intravenous potassium chloride. Blood was sampled 1, 6, 12, and 24 hours after ROSC. Protein and mRNA levels of HIF-1α, VEGF and EPO were detected in the cerebral cortex by immunohistochemistry and real-time RT-PCR; serum levels of NSE and S100β were determined by enzyme-linked immunosorbent assays.
RESULTS: Serum S100β and NSE were significantly increased in the control group versus the sham-operated group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the control rats (P<0.05). Serum NSE and S100β were significantly decreased in the SA group versus the control group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the SA group (P<0.05).
CONCLUSIONS: The expression of HIF-1α is increased in rat cerebral cortex after ROSC, and SA up-regulates the expression of HIF-1α. The up-regulation of HIF-1α improves the resistance of the cortex to ischemia and hypoxia and contributes to neuroprotection, possibly because of up-regulation of EPO and VEGF expression.

Key words: Cardiopulmonary resuscitation, HIF-1α, Erythropoietin, Vascular endothelial growth factor, β-sodium aescinate, Neuroprotection

Jian Kang, Ping Gong, Yan-bo Ren, Dong-na Gao, Qiong-lei Ding. Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation[J]. World Journal of Emergency Medicine, 2013, 4(1): 63-68.

Figures/Tables 3

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Figure 1.

Table 2

References 17

1	de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI, van Ree JW, Daemen MJ, Houben LG, et al. Out-of-hospital cardiac arrest in the 1990's: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 1997; 30:1500-1505.
2	Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Bottiger BW, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008; 118:2452-2483.
3	Gong P, Li CS, Hua R, Zhao H, Tang ZR, Mei X, et al. Mild hypothermia attenuates mitochondrial oxidative stress by protecting respiratory enzymes and upregulating MnSOD in a pig model of cardiac arrest. PLoS One 2012; 7:e35313. pmid: 22532848
4	Fan X, Heijnen CJ, van der Kooij MA, Groenendaal F, van Bel F. The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev 2009; 62:99-108. doi: 10.1016/j.brainresrev.2009.09.006 pmid: 19786048
5	Fan XJ, Guo K, Xiao B, Zi XH, Song Z. Effects of sodium aescinate on bcl-2 and caspase-3 expression and apoptosis after focal cerebral ischemia reperfusion injury in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2005; 30:261-265, 275. pmid: 16045009
6	Du Y, Wang T, Jiang N, Ren RT, Li C, Li CK, et al. Sodium aescinate ameliorates liver injury induced by methyl parathion in rats. Exp Ther Med 2012; 3:818-822. pmid: 22969975
7	Wang Y, Ye Z, Hu X, Huang J, Luo Z. Morphological changes of the neural cells after blast injury of spinal cord and neuroprotective effects of sodium beta-aescinate in rabbits. Injury 2010; 41:707-716. doi: 10.1016/j.injury.2009.12.003 pmid: 20060971
8	Idris AH, Becker LB, Ornato JP, Hedges JR, Bircher NG, Chandra NC, et al. Utstein-style guidelines for uniform reporting of laboratory CPR research. A statement for healthcare professionals from a task force of the American Heart Association, the American College of Emergency Physicians, the American College of Cardiology, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine. Writing Group. Circulation 1996; 94:2324-2336.
9	Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002; 64:993-998. doi: 10.1016/s0006-2952(02)01168-1 pmid: 12213597
10	Mu D, Jiang X, Sheldon RA, Fox CK, Hamrick SE, Vexler ZS, et al. Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model. Neurobiol Dis 2003; 14:524-534. doi: 10.1016/j.nbd.2003.08.020 pmid: 14678768
11	Moser KV, Humpel C. Vascular endothelial growth factor counteracts NMDA-induced cell death of adult cholinergic neurons in rat basal nucleus of Meynert. Brain Res Bull 2005; 65:125-131.
12	Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, et al. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst 2004; 96:946-956. pmid: 15199114
13	Marti HH. Erythropoietin and the hypoxic brain. J Exp Biol 2004; 207:3233-3242. doi: 10.1242/jeb.01049 pmid: 15299044
14	Pacary E, Petit E, Bernaudin M. Erythropoietin, a cytoprotective and regenerative cytokine, and the hypoxic brain. Neurodegener Dis 2006; 3:87-93. doi: 10.1159/000092098 pmid: 16909042
15	Kumral A, Gonenc S, Acikgoz O, Sonmez A, Genc K, Yilmaz O, et al. Erythropoietin increases glutathione peroxidase enzyme activity and decreases lipid peroxidation levels in hypoxic-ischemic brain injury in neonatal rats. Biol Neonate 2005; 87:15-18. pmid: 15334031
16	Maiese K, Li F, Chong ZZ. Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 2004; 25:577-583. pmid: 15491780
17	Kim MS, Seo YK, Park HJ, Lee KH, Choi EJ, Kim JK, et al. The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats. Korean J Pediatr 2010; 53:898-908. pmid: 21189961

Variables	Time after ROSC
Variables	1 h	6 h	12 h	24 h
S100β (ng/mL)
Sham	0.002±0.001	0.003±0.001	0.002±0.002	0.002±0.001
Control	0.234±0.108^*	0.603±0.210^*	0.364±0.137^*	0.324±0.126^*
SA	0.132±0.098^#	0.335±0.127^#	0.211±0.099^#	0.193±0.107^#
NSE (ng/mL)
Sham	2.113±0.102	2.125±0.904	2.103±0.936	2.099±0.101
Control	2.879±0.859	4.483±1.022^*	5.691±1.124^*	8.834±1.457^*
SA	2.691±0.121	3.276±0.973^#	3.961±1.003^#	5.074±1.341^#

Variables	Time after ROSC
Variables	1 h	6 h	12 h	24 h
HIF-1α mRNA
Sham	0.093±0.025	0.098±0.028	0.108±0.027	0.096±0.029
Control	0.094±0.023	0.344±0.063^*	0.767±0.057^*	1.243±0.056^*
SA	0.120±0.012	0.598±0.091^#	1.205±0.135^#	1.629±0.164^#
EPO mRNA
Sham	0.122±0.018	0.114±0.018	0.119±0.017	0.117±0.019
Control	0.115±0.016	0.331±0.093^*	0.682±0.248^*	1.223±0.065^*
SA	0.115±0.029	0.610±0.091^#	1.211±0.131^#	1.582±0.189^#
VEGF mRNA
Sham	0.033±0.016	0.035±0.013	0.036±0.014	0.034±0.012
Control	0.037±0.017	0.046±0.018^*	0.096±0.036^*	0.117±0.021^*
SA	0.041±0.015	0.640±0.025^#	0.117±0.018^#	0.153±0.029^#

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