精准医学杂志 (Dec 2023)
PROTECTIVE EFFECT OF NEUREGULIN1β ON OXYGEN-GLUCOSE DEPRIVATION/REOXYGENATION-INDUCED PC12 CELL INJURY AND ITS MECHANISM
Abstract
Objective To investigate the protective effect of neuregulin1β (NRG1β) on PC12 cell injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and its mechanism. Methods OGD/R models of PC12 cells were established and randomly divided into control group (routinely cultured), model group (OGD/R-treated), and intervention group (treated with OGD/R and intervened by NRG1β). The cell viability of each group was measured by cell counting kit-8. The levels of reactive oxygen species (ROS) were measured by fluorescence intensity analysis. The levels of malondialdehyde (MDA) and the absorbance ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) were measured by fluorescence spectrophotometry. Mitochondrial damage in each group was observed under a transmission electron microscope. The expression of glutathione peroxidase 4 (GPX4) was measured by Western blot. Results Compared with the control group, the model group had significantly decreased cell viability (t=25.76,P<0.01), a significantly increased ROS level (t=12.43,P<0.01), a significantly decreased absorbance ratio of GSH/GSSG (t=9.17,P<0.01), and a significantly increased MDA level (t=29.46, P<0.01). Compared with the model group, the intervention group showed significantly increased cell viability (t=8.03,P<0.01), a significantly decreased ROS level (t=10.34,P<0.01), a significantly increased absorbance ratio of GSH/GSSG (t=15.71,P<0.01), and a significantly decreased MDA level (t=2.96,P<0.05). Transmission electron microscopy results showed that mitochondrial damage was increased in the model group compared with the control group, and NRG1β intervention alleviated mitochondrial damage. Western blot analysis showed that the GPX4 protein expression was significantly lower in the model group than in the control group (t=23.06,P<0.01), and significantly higher in the intervention group than in the model group (t=6.07,P<0.05). Conclusion NRG1β can alleviate PC12 cell injury induced by OGD/R through regulating the expression of GPX4, a key protein of ferroptosis.
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