The neuroprotective role of SIRT1/PGC-1α signaling in limb postconditioning in cerebral ischemia/reperfusion injury.

Autor: Li L; Department of Nephrology, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China., Zhi D; Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China; Department of Neurology, Changyuan People's Hospital, Changyuan, 453400, China., Cheng R; Department of Cardiology, Changyuan People's Hospital, Changyuan, 453400, China., Li J; Department of Cardiology, The 924th Hospital of Chinese People's Liberation Army Joint Service Support Force, Guilin, China., Luo C; Department of Neurology, Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 510080, China., Li H; Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China. Electronic address: lihao_glmc@163.com.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2021 Apr 01; Vol. 749, pp. 135736. Date of Electronic Publication: 2021 Feb 15.
DOI: 10.1016/j.neulet.2021.135736
Abstrakt: Limb ischemic postconditioning (LPostC) is an innovative treatment for ischemia/reperfusion injury (IRI). However, its mechanisms have not yet been elucidated. Herein, we assessed the importance of SIRT1/PGC-1α signaling in LPostC neuroprotection following cerebral I/R injury in rats. In this study, we used 40 male SD rats that were separated into sham, I/R, LPostC, and LPostC + EX-527 (SIRT1 inhibitor) groups (each with 10 rats), with a middle cerebral artery occlusion (MCAO) model used to induce IRI. LPostC was induced via three cycles of bilateral femoral artery occlusion and non-occlusion. At 24 h, we examined SIRT1 and PGC-1α protein levels by western blotting in ischemic areas. The mRNA levels of SIRT1, PGC-1α, NRF-1 and CytoC1 in the ischemic area were assessed by qRT-PCR. We also quantified neurological deficit scores and evaluated cerebral infarct volume by TTC staining. TUNEL staining was used to evaluate the apoptotic rates in neurons. In addition, antioxidant SOD activity and MDA levels were measured by the Microplate Reader. Our findings indicated that LPostC increased the protein and mRNA levels of SIRT1 and PGC-1α in cerebral ischemic tissue, then up-regulated the downstream protein NRF-1, down-regulated CytoC1, and improved mitochondrial function, thereby reducing brain damage. LPostC relieved cerebral IRI via reducing the size of the cerebral infarct, neuronal apoptosis, and neurological deficits. Meanwhile LPostC increased SOD activity and reduced MDA content in brain tissue. Treatment with EX-527 reversed the protection of LPostC after IRI (all P < 0.05). This suggests that LPosC may protect against cerebral IRI at least in part via up-regulating the SIRT1/PGC-1α signaling pathway, thereby increasing the individual's ability to resist oxidative stress.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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