The Role Of Nur77 And GRP78 In Diabetic Myocardial Ischemia Reperfusion Injury

Objective:To investigate the role of GRP78 and Nur77 in myocardial ischemia-reperfusion injury in diabetic rats.Methods:114healthymale SD rats were selected and 100 were randomly selected for the establishment of diabetic rat model by chemical induction method,and 55 rats were successfully constructed.Forty-two of them were randomly selected to establish the ischemia-reperfusion model(I/R)of the heart by ligating the left anterior descending coronary artery,and a total of 37 were successfully established,of which 18 were only reperfusion for 50 minutes(I/R50 group);19 were only 120 minutes of reperfusion(I/R120 group);The other 13 diabetic model rats were Sham group(the diabetes control group).The other 14 healthy rats were the normal control group(N),both Sham group and the N group passed a suture line under the left anterior descending coronary artery without ligation.Echocardiography was performed before and 2 hours after the operation,respectively;Cardiac specimens were collected 5 hours after the rats were put to death,and suborganelles were isolated by differential centrifugation.The expressions of GRP-78 and Nur-77 proteins in the nucleus and cytoplasm were detected by Western blot.Results:In the diabetic group,blood glucose significantly increased;Echocardiography results showed that there were no significant differences in LVEF,LVFS,and LVEDd between the groups before surgery(all P>0.05).Two hours after surgery,compared with sham group,LVEF and LVFS in the I/R 50 group were significantly decreased(P<0.05)and LVEDd was significantly increased(P<0.05).Meanwhile,LVEF and LVFS in the I/R120 group were significantly decreased(P<0.05),and LVEDd was significantly increased(P<0.05).Compared with I/R50,LVEF and LVFS in group I/R 120 were slightly decreased,but there was no statistical significance(P>0.05),and LVEDd was not significantly different(P>0.05).Compared with group I/R50,LVEF in group I/R120 decreased significantly after surgery,while LVFS no significantly in group I/R120;In mitochondria,compared with sham group,GRP78 and Nur77 contents in group I/R50 were significantly increased(P<0.05),and GRP78 and Nur77 contents in group I/R 120 were also significantly increased(P<0.05).There was no significant difference in GRP78 and Nur77 levels between I/R 120 group and I/R50 group(P>0.05).There was no statistically significant difference in mitochondrial contents between GRP78 and Nur77 in sham group and N group(P>0.05).In the nucleus,Nur77 was lowly expressed in group I/R50(P<0.05)and in group I/R 120(P<0.05),compared with sham group.There was no significant difference between I/R50 group and I/R 120 group(P>0.05).There was no significant difference in Nur77 expression between sham group and N group(P>0.05).In the endoplasmic reticulum,GRP78 expression was lower in group I/R50 than in sham group(P<0.05),and lower in group I/R 120 than in sham group(P<0.05).There was no significant difference between I/R50 group and I/R 120 group(P>0.05).There was no significant difference in GRP78 expression between sham group and N group(P>0.05).Conclusion:During ischemia-reperfusion in diabetic rats,mitochondrial targeted translocation demonstrated by GRP78 and Nur77 may be involved in myocardial apoptosis and lead to myocardial ischemia-reperfusion injury.