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Medical Science Monitor Basic Research


eISSN: 1643-3750

Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

Zhen Zhang, Xin Chen, Sichen Liu

Department of Pediatrics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China (mainland)

Med Sci Monit 2020; 26:e924544

DOI: 10.12659/MSM.924544

Available online: 2020-06-22

Published: 2020-08-22


BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is a dreaded disease and one of the leading causes of severe neurological dysfunction in neonates. The present study explored the functions of Sirtuin-1 (SIRT1) in neonatal HIE.
MATERIAL AND METHODS: A HIE neonatal rat model was generated to determine SIRT1 levels in brain tissues. Cell apoptosis and cell viability were analyzed by flow cytometry and MTT assay. qRT-PCR and Western blot analysis were used to assess gene mRNA and protein levels. Subsequently, the effect of SIRT1 on HIE was investigated in vitro by constructing an oxygen-glucose deprivation (OGD) cell model.
RESULTS: The effective construction of the HIE rat model was confirmed by the enhanced brain cell apoptosis and the increased expression of HIE-related molecular markers, including S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE). SIRT1 expression was downregulated in HIE rat brain tissues. These findings indicated that SIRT1 was downregulated in neuronal cells subjected to OGD. In addition, enhanced cell viability and reduced cell apoptosis were observed, suggesting that SIRT1 overexpression relieved OGD-induced neuronal cell injury. Transfection with SIRT1-siRNA further increased OGD-induced neuronal cell injury, evidenced by decreased cell viability and enhanced cell apoptosis. Finally, SIRT1 overexpression significantly downregulated p-p65 protein expression.
CONCLUSIONS: Our findings revealed that SIRT1 may be a novel and promising therapy target for HIE treatment.

Keywords: Hypoxia-Ischemia, Brain, Neurons, sirtuin 1