| Objective: To observe the effect of naringenin on cardiac injury in ischemia/reperfusion(I/R)rats,and 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,ischemia/reperfusion(I/R)group,naringenin+I/R(NAR)group and naringenin+LY294002+I/R(NL)group,with 12 rats in each group.Myocardial I/R injury model was prepared by ligation of left anterior descending coronary artery of rats.Sham group: The thread was threaded under the left anterior descending coronary artery without ligation after thoracotomy.I/R group: The left anterior descending coronary artery was ligated for 30 minutes and followed by reperfusion for 120 minutes.NAR group: Naringenin(100mg/kg)was injected intraperitoneally once a day one week before modeling,and the rest steps were the same as those in the I/R group.NAR group: Naringenin(100mg/kg)was injected intraperitoneally once a day one week before modeling,and LY294002(0.3mg/kg)was injected intraperitoneally 30 minutes before modeling.The rest steps were the same as those in the I/R group.After reperfusion,the abdominal aortic blood and heart tissue of rats were collected to detect the related indexes.The concentration of cardiac troponin I(c Tn I)in serum 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 apoptosis rate.The m RNA expression of endoplasmic reticulum stress-related indicators(GRP78,CHOP and caspase-12)were detected by RT-q PCR.The protein expressions of cleaved caspase-3,GRP78,CHOP,caspase-12,p-PI3 K and p-AKT were detected by Western blot.Results:(1)Compared with the Sham group,the concentration of c Tn I was significantly increased(P<0.05),and the pathological morphology of myocardial tissue was changed(P<0.05),and myocardial infarction area was significantly increased(P<0.05)in the I/R group.Pre-treatment with naringenin could remarkably alleviate the cardiac injury caused by I/R(P<0.05).The cardioprotective effect of naringenin was partially abrogated by pre-administration of LY294002(P<0.05).(2)Compared with the Sham group,the green fluorescence of apoptotic cells and myocardial cell apoptosis rate was increased(P<0.05),and the expression of cleaved caspase-3 was up-regulated(P<0.05)in the I/R group.Pre-treatment with naringenin could remarkably attenuate the apoptosis of myocardial cells induced by ischemia/reperfusion(P<0.05).The antiapoptotic effect of naringenin was partially abolished by pre-administration of LY294002(P<0.05).(3)Compared with the Sham group,the expression of endoplasmic reticulum stress-related indicators GRP78,CHOP and Caspase-12 were significantly increased in the I/R group(P<0.05),suggesting that myocardial I/R injury could induce endoplasmic reticulum stress response and activate endoplasmic reticulum stress-related apoptosis pathways.Pre-treatment with naringenin could inhibited the upregulation of GRP78,CHOP and Caspase-12(P<0.05),suggesting that naringenin could improve endoplasmic reticulum stress and its related apoptotic pathways induced by myocardial I/R injury.Pre-administration of LY294002 could partially block the inhibitory effect of naringenin on endoplasmic reticulum stress and its related apoptotic pathways(P<0.05).(4)Compared with the Sham group,the expression of p-PI3 K and p-AKT were not significantly changed in the I/R group(P>0.05).Pre-treatment with naringenin could remarkably up-regulated the expression of p-PI3 K and p-AKT(P<0.05).Pre-administration of LY294002 could reversed phosphorylation of p-PI3 K and p-Akt by naringenin(P<0.05),suggesting that naringenin may play a cardioprotective role by activating PI3K/Akt signaling pathway during myocardial I/R injury.Conclusion: 1.Pre-treatment with naringenin could alleviate myocardial I/R injury and has a protective effect on the heart of rats in vivo.2.Myocardial I/R injury could induce endoplasmic reticulum stress response and activate endoplasmic reticulum stress-related apoptosis pathway,while pre-treatment with naringenin could improve myocardial I/R injury by inhibiting endoplasmic reticulum stress response and its related apoptosis pathway.3.PI3K/Akt signaling pathway is involved in the protective effect of naringenin on the heart and the inhibitory effect on endoplasmic reticulum stress. |
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