Objective To explore the cardioprotection effect of co-treatment with ischaemic postconditioning and the mechanism of PI3K/Akt signal pathway in ischaemia postconditioning.
Methods 32 healthy adult male Wistar rats were assigned randomly into ischaemia/reperfusion group (I/R), ischaemia postconditioning group (IPost), IPost+Wortmannin group (IPost+W), I/R+ SB216763group (I/R+SB), each group has eight rats. Rats were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischaemia for 30 min followed by 60 min reperfusion. The cardia injury was evaluated by the levels of lactate dehydrogenase (LDH) and Creatine kinase (CK) in the coronary effluent. Ventricular haemodynamic parameters were also measured, include HR, LVSP. Left ventricular myocardial was separated and cut to five slice. After experiment, the myocardial was used for myocardial infarction size evaluated with TTC stained. Immunohistochemical staining for Phosphorylation Akt and GSK-3β expression.
Results Ischemic postconditioning reduced LDH, CK and improved the haemodynamic parameters, and reduced myocardial infarction size (29.5% vs 47.3%). phospho-Akt and phospho-GSK-3β expression increased markedly in IPost group. Wortmannin may reduced phospho-Akt expression, and phospho-GSK-3β expression increased in I/R+SB group.
Conclusion Ischemic postconditioning may synergically protect myocardium in isolated rat heart. Wortmannin, a inhibitor of Akt, may weaken the cardioprotection effect of postconditioning. SB216763, as a inhibitor of GSK-3β, can simulate cardioprotection effect of postconditioning. Akt and GSK-3β play important role in the mechanism of signal pathway in ischaemia postconditioning.
- Ischaemic /reperfusion injury
- ischaemic postonditioning
- Akt pathway