NAC Mitigates ROS Accumulation and NLRP3 Inflammasome-Related Expression and Attenuates Vascular Pyrosis in Intracranial Aneurysms

Abstract

Background: Tissues surrounding ruptured aneurysms exhibit heightened inflammatory activation. Oxidative stress is a pivotal factor in endothelial injury, where moderate and high concentrations of reactive oxygen species induce apoptosis via oxidative stress. Furthermore, oxidative stress and reactive oxygen species have been implicated in vascular smooth muscle cells (VSMC) phenotypic switch and apoptosis. This study aimed to investigate the impact of N-acetyl-L-cysteine (NAC) in a rat aneurysm model subjected to a high salt diet and surgical intervention. Methods: Rats were randomly divided into four groups: normal control, surgery alone, surgery with low-dose NAC, and surgery with high-dose NAC. A cerebral aneurysm model was induced in the latter three groups by ligating the posterior branches of bilateral renal arteries and the left common carotid artery and administering a high salt (8% NaCl) diet for 3 months. The control group received a high salt (8% NaCl) diet only. Inflammatory factor levels were assessed using enzyme-linked immunosorbent assay (ELISA), and related protein expression was examined via western blot. Results: Treatment with NAC significantly delayed the progression of cerebral aneurysms, exerting an inhibitory effect on inflammation. Expression levels of nucleotide-binding oligomerization domain, leucine-rich repeats and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speckled protein (ASC), Caspase-1, interleukin-6 (IL-6), and tumor necrosis factor (TNF) proteins in cerebral aneurysm tissues were markedly reduced. NAC treatment led to a significant decrease in reactive oxygen species (ROS) levels, particularly in the high-dose group. Transmission electron microscopy of the ultrastructure of the cells in each group revealed that cells in the aneurysms of the model group were charred and dead, while those in the arterial tissues of the NAC group exhibited intact nuclei and cytoplasm with rounded edges. Conclusion: NAC can diminish ROS production in cerebral aneurysm model rats, attenuating the oxidative stress and inflammatory response in cerebral aneurysms. This effect contributes to the reduction and delayed onset of cerebral aneurysms, ultimately improving the prognosis of cerebral aneurysms. Additionally, NAC may partially inhibit the expression process induced by ROS-mediated NLRP3 inflammasome.