Didymin Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the PPAR Signaling Pathway
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Purpose: Cerebral ischemia-reperfusion (IR) injury is a severe secondary injury induced by reperfusion after stroke. Didymin has been reported to have a protective effect on intracerebral hemorrhage. However, the underlying mechanism of didymin on regu lating cerebral IR injury remains largely unknown. Materials and Methods: A rat cerebral IR model and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells were established. Hematoxylin and eosin (H&E) was used to detect the pathological changes in brain tissues, and TUNEL staining was performed to detect apoptosis of brain tissues. MTT and flow cytometry were used to measure the viability and apoptosis of PC12 cells. QRT-PCR and western blot were used to detect inflammation cytokines in PC12 cells. Western blot was used to measure the expression of PPAR-γ, RXRA, Bax, c-caspase-3, and Bcl-2. Results: Didymin pretreatment decreased apoptotic rates, reduced levels of Bax and c-caspase-3, and increased Bcl-2 level in vivo and in vitro. Additionally, didymin pretreatment increased viability and decreased the inflammation levels [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein (MCP)-1] of OGD/R treated PC12 cells. Moreover, did ymin activated the peroxisome proliferator-activated receptors (PPAR) signaling pathway and increased the expression of PPAR-γ and RXRA in OGD/R treated PC12 cells. Inhibition of PPAR-γ eliminated the protective effect of didymin on OGD/R treated cells. Conclusion: Didymin protected neuron cells against IR injury in vitro and in vivo by activation of the PPAR pathway. Didymin may be a candidate drug for IR treatment.
Abstract
Purpose: Cerebral ischemia-reperfusion (IR) injury is a severe secondary injury induced by reperfusion after stroke. Didymin has been reported to have a protective effect on intracerebral hemorrhage. However, the underlying mechanism of didymin on regu lating cerebral IR injury remains largely unknown. Materials and Methods: A rat cerebral IR model and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells were established. Hematoxylin and eosin (H&E) was used to detect the pathological changes in brain tissues, and TUNEL staining was performed to detect apoptosis of brain tissues. MTT and flow cytometry were used to measure the viability and apoptosis of PC12 cells. QRT-PCR and western blot were used to detect inflammation cytokines in PC12 cells. Western blot was used to measure the expression of PPAR-γ, RXRA, Bax, c-caspase-3, and Bcl-2. Results: Didymin pretreatment decreased apoptotic rates, reduced levels of Bax and c-caspase-3, and increased Bcl-2 level in vivo and in vitro. Additionally, didymin pretreatment increased viability and decreased the inflammation levels [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein (MCP)-1] of OGD/R treated PC12 cells. Moreover, did ymin activated the peroxisome proliferator-activated receptors (PPAR) signaling pathway and increased the expression of PPAR-γ and RXRA in OGD/R treated PC12 cells. Inhibition of PPAR-γ eliminated the protective effect of didymin on OGD/R treated cells. Conclusion: Didymin protected neuron cells against IR injury in vitro and in vivo by activation of the PPAR pathway. Didymin may be a candidate drug for IR treatment.
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