Role of SIRT1 in regulating endoplasmic reticulum stress in early brain injury after subarachnoid hemorrhage / 国际生物医学工程杂志

ABSTRACT

Objective:To investigate the effect of Sirtuin 1 (SIRT1) on subarachnoid hemorrhage (SAH) and its possible mechanism.Methods:A mouse model of SAH was constructed by internal carotid artery puncture. The protein and mRNA expression levels of SIRT1 at 0, 3, 6, 12, 24, 48, and 72 h were detected by Western Blot and qRT-PCR. A Western Blot assay was used to examine SIRT1 and the expression levels of endoplasmic reticulum stress-related markers GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP after administration of a SIRT1 inhibitor or SIRT1 si-RNA. At 24 h after SAH, subarachnoid hemorrhage volume, neurological function score, brain water content, and blood-brain barrier integrity were measured.Results:The highest expression of SIRT1 protein and mRNA was observed at 24 h compared with other time points, and the differences were statistically significant (all P < 0.001). Inhibition of SIRT1 expression leads to increased expression of endoplasmic reticulum stress-related proteins GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP, exacerbating hemorrhage and brain water content, disrupting blood-brain barrier integrity, and significantly reducing neurological function scores. Conclusions:Inhibition of SIRT1 expression significantly increased the endoplasmic reticulum response to excitation and exacerbated early brain injury after SAH.