
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 1, 2025
Cerebral ischemia-reperfusion (CIR) injury critically impacts stroke prognosis, yet effective therapeutic strategies remain limited. Irisin, an exercise-induced myokine, exhibits neuroprotective effects against cerebral ischemia. SIRT3, a mitochondrial deacetylase, is similarly implicated in mitigating injury. Given that irisin exerts protection via AMPK/PGC-1α pathway activation and SIRT3 acts downstream of PGC-1α , we hypothesized mediates irisin's neuroprotection CIR In vivo was modeled by inducing transient middle artery occlusion (MCAO) mice, while vitro conditions were replicated using oxygen-glucose deprivation (OGD) PC12 neuronal cultures. To elucidate the mechanistic role targeted interventions implemented: expression silenced transfection with small interfering RNA (siRNA), its enzymatic activity pharmacologically inhibited 3-TYP, selective inhibitor. Apoptotic systematically evaluated through TUNEL staining, Western blot analysis caspase-3, Bax Bcl-2. Oxidative stress parameters, including malondialdehyde (MDA) levels glutathione (GSH) content, measured colorimetric assays. Neurological function mice quantified modified Severity Score (mNSS). Our results demonstrated mitigates apoptosis oxidative dose-dependently activating signaling. At optimal dosage, effectively restored levels, reduced damage, improved neurological recovery models. Notably, significantly attenuated specific Further validation experiments revealed overexpression synergistically enhanced irisin-mediated OGD-induced injury, whereas knockout substantially diminished efficacy. data shown exerted protective at least part, activation. This study establishes irisin/SIRT3 as novel target for ischemic stroke, providing insights future interventions.
Language: Английский