| Objective:The aim for the study is to observe the lesion and apoptosis degrees in acute myocardiai infarction (AMI) rats when dysglycemia, determine whether endoplasmic reticulum stress (ERS)-induced cell death is the potential pathway through which dysglycemia influences the outcome of AMI, and investigate the mechanism of cardiomyocyte apoptosis induced by ERS in AMI rats with dysglycemia so as to provide a new direction to the clinical prevention and treatment of AMI in the futureMethods:1. The clean grade healthy male Wister rats, as experimental animal, were randomly assigned to six groups:(1) hypoglycemia+sham (SL, n=13), (2) normal glucose+ Sham (SN, n=13), (3) hyperglycemia+sham (SH, n=13), (4) hypoglycemia+MI (ML, n=13), (5) normal glucose+MI (MN, n=13), (6) hyperglycemia+MI (MH, n=13). Hypoglycemia and hyperglycemia rats were prepared by intraperitoneal injecting insulin 5 U/kg R and 25% glucose of 1.5g/kg into the animals, respectively. AMI was induced by permanent left anterior descending (LAD) coronary artery ligation. Sham groups underwent the same time matched surgical procedure without ligation.2. The model was assessed using glucose meter and Electrocardiograms (ECG).3. The pathological morphology of the myocardium tissues were observed through the histopathology staining (HE).4. The cell apoptosis rate in the myocardium was determined by TUNEL.5. The nuclear translocation of glucose regulated protein (GRP78), Caspase 12 and C/EBP-homdogous protein (CHOP) were detected by immunohistochemistry analysis,6. Protein and mRNA levels of GRP78, the activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE-1), protein kinase R-like ER kinase (PERK), Caspase 12 and CHOP were examined by Western blot analysis and real time-PCR, respectively.Resultsl.The glucose level in hypo-and hyper-glycemia was<3.6 mmoL/L and>16 mmoL/L, respectively. Animals with blood glucose levels between 5 mmoL/L and 7 mmoL/L were normal. Preoperative and postoperative ST segment in the AMI rats raised slightly and significantly, respectively. And therewas a pathologic Q wave in the ECG of the AMI rats before killed. While the control group of preoperative and postoperative ST segment are not significantly raise.2. HE staining showed that the myocardiai tissue morphology of SN group was close to normal. In SL and SH group, the nuclei were little pyknotic and gathered. In MN group, the nuclei were mildly pyknotic and gathered. However, there were a lot of pyknotic and gathered nuclei in ML and MH group. A little of necrosis also could be found in the edge area of myocardial tissue in ML and MH group.3. There were no significant difference of the apoptosis degrees in myocardium tissues among sham groups (P>0.05). The apoptosis degrees of myocardium tissues in the AM I rats were more serious than sham-group (P<0.05). And in the ML and MH rats, they were more serious than MN (P<0.05).3. Compared with MN group, we found that GRP78 was up-regulated in ML and MH (P<0.05), ATF6 was up-regulated only in ML (P<0.05), IRE-1 was up-regulated in both ML and MH (P<0.05), while there was no change about PERK (P>0.05). We also found that it was CHOP rather than Caspase 12 was up-regulated (P<0.05) in both ML and MH compared with MN group. And there were no significant difference of them in myocardium tissues among sham groups (?>0.05). All of the proteins were up-regulated in AMI compared with sham group (P<0.05).Conclusions Taken together, we have found that the lesion and apoptosis degrees in AMI rats were more serious when dysglycemia And the experiment suggested that ERS-induced cell death is the potential pathway through which dysglycemia influences the outcome of AMI. Hyperglycemia through I RE-1 pathway up-regulated apoptotic factor CHOP to influence the outcome of AMI. Hypoglycemia through I RE-1 and ATF6 pathway up-regulated apoptotic factor CHOP to influence the outcome of AMI. |
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