Remote limb ischemic postconditioning protects focal cerebral ischemia-reperfusion injury in rats via phosphatidylinositol 3 kinase/Akt pathway

Abstract

Objective To investigate the role of phosphatidyl inositol 3 kinase (PI3K)/Akt pathway in the protection of focal cerebral ischemia reperfusion injury in rats with limb ischemic postconditioning (LIP) by detecting the expression levels of p-Akt protein, and caspase-9 and Bcl-2 mRNAs after remote LIP. Methods Forty-two Wistar rats were randomly assigned to 3 groups: sham operation, ischemia-reperfusion (IR) and LIP groups. The middle cerebral artery ischemia-reperfusion injury model was induced by the suture method in the IR group and the LIP group. In the LIP group, three circulatory LIP (5 min ischemia/5 min reperfusion) in the contralateral femoral artery were performed before reperfusion 2 h after cerebral ischemia. Infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride staining. The expression of p-Akt protein was detected by immunohistochemical staining and the expression levels of cystin-9 and Bcl-2 mRNAs were detected by in situ hybridization. Results Compared with the IR group, the infarct volume in the LIP group was significantly reduced (P<0.05). The expression levels of p-Akt protein and Bcl-2 mRNA significantly increased (all P<0.05), and the expression level of caspase-9 mRNA significantly decreased (P<0.05). Conclusions LIP can reduce the volume of cerebral infarction in focal cerebral ischemia-reperfusion injury in rats. Its mechanism may be involved in up-regulation of p-Akt protein and Bcl-2 mRNA expression and down-regulation of caspase-9 mRNA expression, suggesting that LIP can alleviate cerebral ischemia-reperfusion injury through PI3K/Akt pathway. Key words: Brain Ischemia; Reperfusion; Ischemic Postconditioning; Extremities; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Caspase 9; Proto-Oncogene Proteins c-bcl-2; Disease Models, Animal; Rats