摘要目的:评价脓毒症小鼠肺损伤时磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路与血红素氧合酶1(HO-1)表达的关系。方法:清洁级健康雄性C57BL/6小鼠48只，6～8周龄，体重20～25 g，采用随机数字表法分为4组( n＝12)：假手术组(SH组)、脓毒症组(SEP组)、PI3K抑制剂LY294002组(LY组)和PI3K抑制剂LY294002＋HO-1激动剂Hemin组(LH组)。采用盲肠结扎穿孔法制备脓毒症诱发小鼠肺损伤模型。LY组及LH组于造模前2 h腹腔注射LY294002 30 mg/kg，LH组于造模前1 h腹腔注射Hemin 50 μmol/kg。术后24 h时处死小鼠取肺，确定肺湿重/干重(W/D)比值，观察肺组织病理学结果并行肺损伤评分，采用ELISA法测定TNF-α和IL-10含量，采用Western blot法检测p-Akt、Akt和HO-1的表达。 结果:与SH组比较，SEP组、LY组和LH组肺W/D比值、肺损伤评分、TNF-α和IL-10含量升高，SEP组肺p-Akt和HO-1表达上调( P<0.05)；与SEP组比较，LY组肺W/D比值、肺损伤评分、TNF-α含量升高，IL-10含量降低，p-Akt和HO-1表达下调( P<0.05)；与LY组比较，LH组肺损伤评分和TNF-α含量降低，IL-10含量升高，HO-1表达上调( P<0.05)。 结论:PI3K/Akt信号通路通过调控HO-1表达参与脓毒症小鼠肺损伤的内源性保护机制。

abstractsObjective: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.