Relationship between PI3K/Akt signaling pathway and HO-1 expression during lung injury in septic mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and heme oxygenase-1 (HO-1) expression during lung injury in septic mice.Methods:Forty-eight clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group SH), sepsis group (group SEP), PI3K inhibitor LY294002 group (group LY) and LY294002+ HO-1 agonist hemin group (group LH). Sepsis was induced by cecal ligation and puncture in anesthetized animals.LY294002 30 mg/kg was intraperitoneally injected at 2 h before establishing the model in LY group and LH group.Hemin 50 μmol/kg was intraperitoneally injected at 1 h before establishing the model in LH group.Mice were sacrificed at 24 h after surgery, and lungs were removed for determination of wet/dry weight ratio (W/D ratio), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents (by enzyme-linked immunosorbent assay), and expression of phosphorylated Akt(p-Akt), Akt and HO-1 (by Western blot) and for examination of the pathological changes of lung tissues which were scored. Results:Compared with SH group, the W/D ratio, lung injury score, and TNF-α and IL-10 contents were significantly increased in SEP, LY and LH groups, and the expression of p-Akt and HO-1 was significantly up-regulated in SEP group ( P<0.05). Compared with SEP group, the W/D ratio, lung injury score and TNF-α content were significantly increased, IL-10 content was decreased, and the expression of p-Akt and HO-1 was down-regulated in LY group ( P<0.05). Compared with LY group, the lung injury score and TNF-α content were significantly decreased, IL-10 content was increased, and the expression of HO-1 was up-regulated in LH group ( P<0.05). Conclusion:PI3K/Akt signaling pathway is involved in the endogenous protective mechanism of lung injury by regulating HO-1 expression in septic mice.