Effects of naringenin on PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways in rats with myocardial ischemia/reperfusion injury |
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Authors: | LAN Zhuo WANG Huan HE Xi-song YOU Li-ping XU Nan FENG Jian LI Jia-fu |
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Affiliation: | Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China |
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Abstract: | AIM To observe the effect of naringenin on cardiac injury in ischemia/reperfusion (I/R) rats, and to explore whether the role of naringenin is involved in PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways. METHODS SD rats (n=48) were randomly divided into sham operation (sham) group, model (I/R) group, naringenin treatment (NAR) group and naringenin+LY294002 (NL) group. Myocardial I/R injury model was prepared by ligation of left anterior descending coronary artery of rats for 30 min followed by reperfusion for 120 min. After reperfusion, the serum levels of cardiac troponin I (cTnI) was measured by ELISA. HE staining, TTC staining and TUNEL staining were used to detect the myocardial histopathological changes, myocardial infarction area and myocardial cell apoptotic rate. The mRNA levels of endoplasmic reticulum stress-related indicators glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 were detected by RT-qPCR. The protein levels of cleaved caspase-3, GRP78, CHOP, caspase-12, p-PI3K and p-AKT were determined by Western blot. RESULTS Compared with I/R group, the serum content of cTnI, myocardial pathological damage, myocardial infarction area and myocardial cell apoptotic rate were significantly reduced (P<0.05), the protein levels of cleaved caspase-3, GRP78, CHOP and caspase-12 were decreased (P<0.05), and the protein levels of p-PI3K and p-AKT were increased in NAR group (P<0.05). LY294002 attenuated the protective effect of naringenin to some extent. CONCLUSION Naringenin reduces myocardial I/R injury in rats possibly by activating PI3K/AKT signaling pathway and subsequently regulating endoplasmic reticulum stress and its related apoptotic pathways. |
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Keywords: | Naringenin Myocardial ischemia Reperfusion injury Endoplasmic reticulum stress Apoptosis PI3K/AKT signaling pathway |
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