Inhibition Of Autophagy Via Activation Of Pi3k/Akt/Mtor Pathway Contributes To The Protection Of Hesperidin Against Myocardial Ischemia/Reperfusion Injury
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE(2018)
Abstract
Hesperidin has been reported to attenuate myocardial ischemia/reperfusion (I/R) injury; however, its effect on autophagy during myocardial I/R and the underlying mechanism remains unknown. The present study aimed to investigate whether hesperidin inhibited PR-induced excessive myocardial autophagy through activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Male adult rats were pretreated with hesperidin for a total of 3 days prior to ischemia in the absence or presence of LY294002, a PI3K inhibitor, and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Myocardial infarct size was measured by Evans blue/triphenyltetrazolium chloride staining. Hematoxylin and eosin staining was used for observing the histological changes in the heart, and the serum levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) were measured by enzyme-linked immunosorbent assay. Additionally, the protein levels of light chain (LC) 3II, Beclinl, phosphorylated (p)-mTOR, p-Akt and p-PI3K were determined by western blot analysis. Hesperidin pretreatment significantly decreased the myocardial infarct size, myocardial damage and serum levels of CK-MB and cTnI. Furthermore, the expression levels of LC3II and Beclinl were significantly downregulated and the expression levels of p-mTOR, p-Akt and p-PI3K were markedly upregulated by hesperidin. However, the aforementioned effects as a result of hesperidin were significantly reversed by the presence of LY294002. These results demonstrated that hesperidin reduced myocardial I/R injury by suppressing excessive autophagy. Activation of the PI3K/Akt/mTOR pathway contributed to the inhibitory effect of hesperidin on excessive autophagy.
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Key words
autophagy, hesperidin, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, myocardial ischemia/reperfusion injury, LY294002
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