Based on the PINK1/Parkin signaling pathway, the protective effect of salidroside on cerebral ischemia-reperfusion injury in male rats was investigated

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OBJECTIVE: Based on the male Sprague-Dawley rats middle cerebral artery occlusion model and SH-SY5Y hypoxia-reoxygenation model, this study systematically evaluated the neuroprotective effect of salidroside (SAL) on cerebral ischemia/reperfusion injury in rats, and explored its possible protective mechanism through PINK1/Parkin signaling axis regulating mitochondrial autophagy. MATERIALS AND METHODS: Using the middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats and the SH-SY5Y cell hypoxia-reoxygenation model, we assessed neurological damage severity through the modified neurological severity scores (NSS). Brain histopathological changes were evaluated using hematoxylin-eosin staining, while the infarct volume in the ischemic brain was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Transmission electron microscopy was employed to observe mitochondrial ultrastructural alterations in the ischemic brain tissue. Western blotting was used for quantitative analysis of key autophagy-related molecules (PINK1, Parkin), and ROS, MDA, and ferrous ion kit were utilized to evaluate ferroptosis biomarker. RESULTS: The findings indicate that SAL effectively reduces infarction rates and ameliorates histopathological changes. SAL decreases the formation of reactive oxygen species, malondialdehyde, and ferrous ions by upregulating the expression of PINK1 and Parkin proteins, thereby mitigating apoptosis. Furthermore, SAL significantly inhibits ferroptosis in SH-SY5Y neuroblastoma cells subjected to OGD/R and reduces oxidative stress. The application of the mitochondrial autophagy inhibitor Mdivi-1 enhances the protective effect of SAL against ferroptosis in both MCAO and OGD/R models. Therefore, we draw the following conclusions: In the rat cerebral ischemia-reperfusion injury model and the SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, iron death was found to be increased. Pre-treatment with salidroside was able to reduce the occurrence of iron death in both the cerebral ischemia-reperfusion injury model and the cellular OGD/R model. CONCLUSIONS: Salidroside may inhibit iron death by activating the PINK 1 / Parkin signaling pathway and thereby reduce cerebral ischemia-reperfusion injury. Targeted regulation of this pathway may become an important strategy to interfere with CIRI.

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