Role of phosphatase and tensin homologue deleted on chromosome ten regulated Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in the sensitivity of ischemic postconditioning to diabetic rat hearts

Abstract

Objective To investigate the role of phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulated Janus kinase2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway in the sensitivity of ischemic postconditioning (IPO) to diabetic hearts. Methods Healthy male SD rats, weighing 220-280 g, were used in this study. Type 1 diabetic rat models were induced by a single intraperitoneal injection of streptozotocin (60 mg/kg), and 8 weeks after, sixty diabetic rats were randomly divided into 5 groups (n=12 each): sham group (S group), ischemia reperfusion group (I/R group), ischemic postconditioning group (IPO group), PTEN inhibitor BpV+I/R group (BpV+I/R group) and BpV+IPO group. Myocardial I/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. IPO was induced by 3 cycles of 10 second reperfusion and ischemia at the onset of reperfusion. Sham group was performed all the steps only not to draw the suture. Bpv (1 mg/kg) was given as intravenous injections 1 hour before ischemia, and the equal volume of normal saline was given in untreated control groups. At 2 hours of reperfusion, the serum and heart tissue of diabetic rats were collected for determination of the level of serum creatine kinase-myocardial band isoenzyme (CK-MB), infarct size (IS), apoptosis index (AI) and PTEN activity, as well as the expression of PTEN, phosphorylated JAK2(p-JAK2), phosphorylated STAT3(p-STAT3) and apoptosis related protein caspase-3. One-way analysis of variance was used when data were compared among multiple groups, paired t test was applied to compare between two groups. Results Compared with S group, the level of CK-MB, PTEN activity were significantly increased, the expression of PTEN and cleaved caspase-3 were up-regulated in both I/R and IPO groups (t=2.997-7.702, all P<0.05). Compared with IPO group, the level of CK-MB, IS and AI, as well as PTEN activity were significantly decreased, and the expression of p-JAK2, p-STAT3 were up-regulated, the expression of cleaved caspase-3 was down-regulated in BpV+IPO group[3 003±613 vs 1 247±440, 42%±8% vs 53%±6%, 21%±3% vs 33%±6%,(584±78) vs (918±136) pmol, 1.73±0.29 vs 1.06±0.24, 1.75±0.19 vs 1.01±0.16, 1.6±0.4 vs 2.2±0.5, t=2.837-9.249, all P<0.05]. There was no significant difference in the parameters mentioned above between I/R and IPO groups, and between BpV+I/R and I/R groups. Conclusion Inhibition of PTEN restores IPO-induced cardioprotection in diabetic reperfusion heart possibly by activating JAK2/STAT3 signaling pathway. Key words: Diabetes mellitus, type 1; Phosphatase and tensin homologue deleted on chromosome ten; Signal transducer and activator of transcription 3; Myocardial reperfusion injury