Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress – induced mitochondrial injury

다국어 초록 (Multilingual Abstract)

Background: Effective strategies are dramatically needed to prevent and improve the recovery frommyocardialischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum(ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotectiveeffects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury,and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored.
Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects ofGP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactiveoxygen species production, and respiratory function were determined using fluorescence detection kitson mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects ofGP-17 on hypoxia/reoxygenation.
Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improvescontractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantlymediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotectiveeffects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways.
Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress throughthe PI3K/AKT and P38 signaling pathways.

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