Relationship between DJ-1 and diabetes mellitus-caused influence on cardioprotection induced by ischemic postconditioning in rats

Abstract

Objective To evaluate the relationship between DJ-1 and diabetes mellitus (DM) -caused influence on cardioprotection induced by ischemic postconditioning in rats. Methods Adult male Sprague-Dawley rats, aged 3 months, weighing 220-250 g, were used in the study.DM was induced by intraperitoneal injection of 1% streptozotocin 60 mg/kg and confirmed by blood glucose≥16.7 mmol/L.Forty-eight rats with DM were randomly divided into 3 groups (n=16 each) using a random number table: sham operation group (group DM-S) , myocardial ischemia-reperfusion (I/R) group (DM-IR) and ischemic postconditioning group (DM-IPO group) . Another 48 normal rats received the equal volume of citrate buffer solution instead and served as control.Those rats were randomly divided into 3 groups (n=16 each) using a random number table: sham operation group (S group) , myocardial I/R group (IR group) and ischemic postconditioning group (IPO group) . At 12 weeks after streptozotocin injection, myocardial I/R was produced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.Ischemic postconditioning was induced by 3 cycles of 10 s reperfusion followed by 10 s limb ischemia at the end of 30 min limb ischemia.At 120 min of reperfusion, the animals were sacrificed, and hearts were removed for determination of myocardial infarction size (using TTC) , and expression of DJ-1, phosphatase and tensin homologue (PTEN) protein, and phosphorylated Akt (p-Akt) in myocardial tissues (by Western blot) . Results The infarction size was significantly increased in diabetic and nondiabetic rats during myocardial I/R.The expression of DJ-1, PTEN protein and p-Akt was significantly higher during myocardial I/R in nondiabetic rats, and the expression of PTEN protein and p-Akt was up-regulated, and no significant change was found in DJ-1 expression during myocardial I/R in diabetic rats.Ischemic postconditioning reduced infarction size during myocardial I/R and up-regulated the expression of DJ-1 and p-Akt, and down-regulated the expression of PTEN protein in nondiabetic rats, but not in diabetic rats.Compared with nondiabetic rats, the expression of DJ-1 and p-Akt was down-regulated, and the expression of PTEN protein was up-regulated after ischemic postconditioning in diabetic rats. Conclusion The mechanism by which DM abolishes cardioprotection induced by ischemic postconditioning is associated with down-regulation of DJ-1 expression in rats. Key words: Diabetes mellitus; Myocardial reperfusion injury; Ischemic postconditioning; DJ-1