Relationship between PI3K/Akt signaling pathway and autophagy during acute lung injury in septic mice

Abstract

Objective To evaluate the relationship between phosphatidylinositol 3-kinase/serine-threonine kinase(PI3K/Akt)signaling pathway and autophagy during acute lung injury in septic mice. Methods Thirty-six male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups(n=12 each)using a random number table: sham operation group(group SH), sepsis group(group S)and PI3K inhibitor LY294002 plus sepsis group(group LY+ S). Sepsis was induced by cecal ligation and puncture in S and LY+ S groups.LY294002 30 mg/kg was intraperitoneally injected at 2 h before operation in group LY+ S.Arterial blood samples were taken at 24 h after operation for blood gas analysis, PaO2 was recorded, and oxygenation index was calculated.Lung specimens were obtained for examination of pathological changes which were scored and for determination of autophagosome count(using transmission electron microscope), wet/dry weight ratio(W/D ratio)and expression of Akt, phosphorylated Akt(p-Akt), Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ). The p-Akt/Akt ratio was calculated. Results Compared with group SH, oxygenation index was significantly decreased, and the W/D ratio and pathological score were increased in S and LY+ S groups, the autophagosome count was significantly increased, p-Akt/Akt ratio was increased, and the expression of Beclin-1 and LC3Ⅱ was up-regulated in group S(P<0.05). Compared with group S, oxygenation index was significantly decreased, and the W/D ratio was increased, the autophagosome count was decreased, pathological scores were increased, p-Akt/Akt ratio was decreased, and the expression of Beclin-1 and LC3Ⅱ was down-regulated in group LY+ S(P<0.05). Conclusion PI3K/Akt signaling pathway activation mediates autophagy and is involved in the endogenous protective mechanism of acute lung injury in septic mice. Key words: 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; Autophagy; Sepsis; Respiratory distress syndrome, adult