Role of phosphoglycerate mutase 5 in myocardial ischemia-reperfusion injury in diabetic rats: relationship with mitochondrial quality / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of phosphoglycerate mutase 5 (phosphoglycerate mutase family member 5, PGAM5) in myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the relationship with mitochondrial quality.Methods:SPF healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type 1 diabetes mellitus was induced by 1% streptozotocin diluted in citrate buffer solution 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Seventy-two rats with type 1 diabetes mellitus were divided into 4 groups ( n=18 each) by a random number table method: diabetic sham operation group (DS group), diabetic myocardial I/R group (DIR group), diabetic myocardial I/R plus AAV9-PGAM5 shRNA group (DIR+ PGAM5 shRNA group), and diabetic myocardial I/R plus AAV9-GFP group (DIR+ GFP group). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h starting from 8 weeks after establishment of type 1 diabetes mellitus model.AAV9-PGAM5 shRNA and AAV9-GFP 2×10 12 μg/kg were slowly injected via tail vein 3 weeks before ischemia.In group AAV9-PGAM5 shRNA, left ventricular systolic pressure (LVSP) and the maximum rate of increase or decrease in left ventricular systolic pressure (±dp/dt max) were monitored and recorded at the end of reperfusion, and then blood samples from the the right carotid artery were collected for determination of serum troponin Ⅰ(cTnI), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). The animals were sacrificed and hearts were obtained for determination of myocardial infarct size (by Evans Blue plus TTC double staining method) and expression of PGAM5, autophagy-related proteins (LC3B, p62), dynamin-related protein 1 (Drp1), and mitochondrial autophagy receptor protein (FUNDC1) (by Western blot) and for microscopic examination of pathological changes of myocardial tissues (by HE staining). Results:Compared with group DS, the LVSP and ±dp/dt max were significantly decreased, the serum levels of cTnI, CK-MB and LDH were increased, myocardial infarct size was increased, the expression of PGAM5, LC3B, Drp1 and FUNDC1 was up-regulated, and the expression of p62 was down-regulated in group DIR and group DIR+ GFP ( P<0.05). Compared with group DIR, LVSP and ±dp/dt max were significantly increased, the serum levels of cTnI, CK-MB and LDH were decreased, myocardial infarct size was decreased, the expression of PGAM5, LC3B, Drp1 and FUNDC1 was down-regulated, and the expression of p62 was up-regulated in group DIR+ PGAM5 shRNA ( P<0.05), and no significant change was found in the parameters mentioned above in group DIR+ GFP ( P>0.05). Conclusion:PGAM5 is involved in the myocardial I/R injury in diabetic rats, which is related to the reduction of mitochondrial quality.