Effect Of PTEN On Myocardial Ischemic Preconditioning And Postconditioning

Background and AimPhosphatase and tensin homologue deleted chromosome 10(PTEN) is a new discovery tumor suppressor gene. It plays an important way in cell growth, differentiation, apoptosis, signal transmission, etc. In the past yeas, the studies mainly concerned about PTEN in tumors. In recent years, studies have found that PTEN/Akt signaling pathways plays an important role in myocardial remodeling, cardiac hypertrophy, and myocardial ischemia-reperfusion injury. There were reported that application specific drugs to inhibit the activity of the PTEN can reduce the myocardial infarction size, improve heart function. Ischemic preconditioning(IPre) and ischemic postconditioning(IPost) were report to against the ischemia-reperfusion injury and reduce the infarct size. However the potential molecular mechanisms activated have not fully clear. Whether the effect of protection by myocardial ischemic preconditioning and postconditioning is related to the PTEN/Akt signal pathways is lacked to research.In this study, we employed animal models and measured the activity of PTEN and its downstream signaling molecules to study the function of PTEN/Akt signal ways in ischemia-reperfusion injury and discuss the molecular mechanisms of protective by ischemic preconditioning and postconditioning.Methods60 Male SD rat, weight 280-320g, were randomly divided into four groups (n=15). â‘  Sham operation group(Sham group):rats were subjected to the surgical procedures without the left anterior descending(LAD) coronary occlusion; â‘¡ Ischemia-reperfusion group(IR group):30min LAD coronary occlusion and followed by 180min reperfusion; â‘¢ Ischemic preconditioning group(IPre group):before 30min of LAD coronary occlusion, three cycles of LAD isehemia(5min) and reperfusion(5min); â‘£ Ischemic postconditioning group(IPost group):After 30min of LAD coronary occlusion, reperfusion was initiated for 30s followed by 30s reperfusion, repeated for three cycles, then followed by 180min reperfusion. The ECG was recorded during the whole process. Selected 6 rats from each group, at the end of the experiment, the heart was dyed by Evans Blue and TTC to examin the myocardial infarction area. The left 9 rats were extracted venous blood before and after establishing model and removed the ischemic myocardial tissue during finish the experiment. The serum levels of CK and LDH were measured. The mythological characteristics were observed by hematoxylin-eosin staining(HE staining). The expression of PTEN and p-Akt were measured by western blot and immunohistochemistry. The expression of PTEN mRNA was measured by real-time PCR(RT-PCR). The experimental date was analyzed by using SPSS software.Results1. ECG:When LAD coronary occlusion, we can saw the ST segment elevation. After reperfusion the elevating ST segment gradually recovered.2. Area at risk and infarct size:The Sham group had no obvious ischemic and infract. The area at risk was similar in the IR group, IPre group and IPost group(P>0.05). However, compared with the IR group, the tissue necrosis was significantly decreased in IPre group and IPost group(P<0.05).3. Serum creatine kinase(CK) and lactate dehydrogenase(LDH) activity:The serum levels of both CK and LDH were no statistical differences among the four groups at baseline(P>0.05). The plasma CK and LDH activity at the end of reperfusion were significantly increased in IR, IPre and IPost group than that in Sham group(P<0.05). However IPre and IPost group reduced the release of CK and LDH compared with the IR group(P<0.05).4. The expression of PTEN, p-Akt:The expression of PTEN was decreased in IPre and IPost group relative to IR group(P<0.05). And compared with the IR group, the expression of p-Akt in IPre and IPost group were enhanced(P<0.05).5.The expression of PTEN mRNA:The level of PTEN mRNA was inhibited in IPre and IPost group compared with the IR group (P<0.05).ConclusionsPTEN/Akt signaling pathway plays an important role in myocardial ischemia-reperfusion injury. Ischemic preconditioning and postconditioning are involved in cardiac protection against ischemia-reperfusion injury through the PTEN/Akt signaling pathway.