脳血管攣縮後の脳保護効果ヘスペリジンにおけるくも膜下出血ラットにおける実験的研究

Subarachnoid hemorrhage (SAH) is a severe neurological emergency with high morbidity and mortality, primarily due to vasospasm and delayed ischemia. Hesperidin (HSP), a natural flavonoid, possesses strong antioxidant and vasoprotective properties. This experimental animal study examined HSP's neuroprotective role in oxidative stress and vascular remodeling after SAH, focusing on the extracellular regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase (Erk5-KLF2-eNOS) pathway.

The study was conducted from 2021 to 2022. Forty female Wistar albino rats were divided into five groups: control (G1, n=8), sham (G2, n=8), SAH + Vehicle (G3, n=8), SAH with low-dose HSP (G4, n=8), and SAH with high-dose HSP (G5, n=8). SAH was induced using a double injection of homologous blood into the cisterna magna. Biochemical markers (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], nitric oxide [NOS]), basilar artery morphometry, and molecular expressions (Erk5, p-Erk5, KLF2, eNOS) were evaluated 48 hours post-SAH.

SAH significantly increased oxidative stress and reduced vascular lumen diameter in untreated rats (G3). Both HSP-treated groups (G4 and G5) showed improved antioxidant enzyme levels (SOD, CAT, GPx) and near-normal NOS levels. Morphometric analysis demonstrated significant preservation of basilar artery lumen diameter in treated groups, with no significant changes in wall thickness. Molecular analysis revealed upregulation of the Erk5-KLF2-eNOS pathway, suggesting a role in vasodilation and mitigation of oxidative stress.

HSP protects against SAH-induced vasospasm and oxidative damage by enhancing antioxidant capacity and modu-lating the Erk5-KLF2-eNOS pathway, suggesting its therapeutic potential.