Effect of irisin on hypoxic-ischemic brain damage in neonatal rats
XU Xuan-Pei1, HUANG Ling-Yi2, ZHAO Feng-Yan1, YING Jun-Jie1, LI Shi-Ping1, YUE Yan1, LI Wen-Xing1, QU Yi1, MU De-Zhi1
Department of Pediatrics, West China Second University Hospital/Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu 610041, China
Abstract:Objective To study the effect and mechanism of action of irisin on hypoxic-ischemic brain damage in neonatal rats. Methods A total of 248 7-day-old Sprague-Dawley rats were randomly divided into a sham-operation group, a model group, and low-and high-dose irisin intervention groups (n=62 each). The rats in the model and irisin intervention groups were given hypoxic treatment after right common carotid artery ligation to establish a model of hypoxic-ischemic brain damage. Those in the sham-operation group were given the separation of the right common carotid artery without ligation or hypoxic treatment. The rats in the high-and low-dose irisin intervention groups were given intracerebroventricular injection of recombinant irisin polypeptide at a dose of 0.30 μg and 0.15 μg respectively. Those in the model and sham-operation groups were given the injection of an equal volume of PBS. The water maze test was used to compare neurological behaviors between groups. TTC staining, hematoxylin-eosin staining and TUNEL staining were used to observe histopathological changes of the brain. Western blot was used to measure the expression of the apoptosis-related molecules cleaved-caspase-3 (CC3), BCL-2 and BAX. Results Compared with the sham-operation group, the model group had a significant increase in latency time and a significant reduction in the number of platform crossings (P P P P P Conclusions Irisin can alleviate hypoxic-ischemic brain damage in neonatal rats in a dose-dependent manner, possibly by reducing cell apoptosis in the cerebral cortex and the hippocampus.
Yıldız EP, Ekici B, Tatlı B. Neonatal hypoxic ischemic encephalopathy:an update on disease pathogenesis and treatment[J]. Expert Rev Neurother, 2017, 17(5):449-459.
[2]
Wassink G, Davidson JO, Dhillon SK, et al. Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy[J]. Curr Neurol Neurosci Rep, 2019, 19(2):2.
[3]
Rao R, Trivedi S, Vesoulis Z, et al. Safety and short-term outcomes of therapeutic hypothermia in preterm neonates 34-35 weeks gestational age with hypoxic-ischemic encephalopathy[J]. J Pediatr, 2017, 183:37-42.
[4]
Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J]. Nature, 2012, 481(7382):463-468.
[5]
Ruan Q, Zhang L, Ruan J, et al. Detection and quantitation of irisin in human cerebrospinal fluid by tandem mass spectrometry[J]. Peptides, 2018, 103:60-64.
[6]
Aydin S, Kuloglu T, Aydin S. Copeptin, adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus[J]. Peptides, 2013, 47:66-70.
[7]
Aydin S, Aydin S, Kuloglu T, et al. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running[J]. Peptides, 2013, 50:13-18.
[8]
Yıldız EP, Ekici B, Tatlı B. Neonatal hypoxic ischemic encephalopathy:an update on disease pathogenesis and treatment[J]. Expert Rev Neurother, 2017, 17(5):449-459.
[9]
Chen K, Xu Z, Liu Y, et al. Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury[J]. Sci Transl Med, 2017, 9(418). pii:eaao6298.
[10]
Siddiqui WA, Ahad A, Ahsan H. The mystery of BCL2 family:Bcl-2 proteins and apoptosis:an update[J]. Arch Toxicol, 2015, 89(3):289-317.
[11]
Charriaut-Marlangue C, Besson VC, Baud O. Sexually dimorphic outcomes after neonatal stroke and hypoxia-ischemia[J]. Int J Mol Sci, 2017, 19(1). pii:E61.
[12]
Zheng Z, Zhang L, Qu Y, et al. Mesenchymal stem cells protect against hypoxia-ischemia brain damage by enhancing autophagy through brain derived neurotrophic factor/mammalin target of rapamycin signaling pathway[J]. Stem Cells, 2018, 36(7):1109-1121.
[13]
Asadi Y, Gorjipour F, Behrouzifar S, et al. Irisin peptide protects brain against ischemic injury through reducing apoptosis and enhancing BDNF in a rodent model of stroke[J]. Neurochem Res, 2018, 43(8):1549-1560.
[14]
Gopagondanahalli KR, Li J, Fahey MC, et al. Preterm hypoxic-ischemic encephalopathy[J]. Front Pediatr, 2016, 4:114.
[15]
Bi J, Zhang J, Ren Y, et al. Irisin alleviates liver ischemia-reperfusion injury by inhibiting excessive mitochondrial fission, promoting mitochondrial biogenesis and decreasing oxidative stress[J]. Redox Biol, 2019, 20:296-306.
[16]
Liao Q, Qu S, Tang LX, et al. Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis[J]. Acta Pharmacol Sin, 2019, 40(10):1314-1321.
[17]
Thornton C, Leaw B, Mallard C, et al. Cell death in the developing brain after hypoxia-ischemia[J]. Front Cell Neurosci, 2017, 11:248.
[18]
Thornton C, Hagberg H. Role of mitochondria in apoptotic and necroptotic cell death in the developing brain[J]. Clin Chim Acta, 2015, 451(Pt A):35-38.
[19]
Walensky LD. Targeting BAX to drug death directly[J]. Nat Chem Biol, 2019, 15(7):657-665.