中文摘要：

目的探讨磷脂酰肌醇3激酶／蛋白激酶B（PI3K／PKB信号转导通路在重症急性胰腺炎肺损伤的表达和意义。方法健康雄性长白猪24只，随机分为假手术组、急性肺损伤（ALI）组、ALI＋内毒素（LPS）组和ALI＋Wortmannin（PI3K抑制剂）组，每组6只。逆行聚合酶链反应（RT-PCR）、免疫印迹方法检测肺组织PI3K／PKBmRNA和PKB白活性，凝胶电泳迁移滞留试验（EMSA）法检测核转录因子-κB（NF—κB）活性变化，酶联免疫法检测肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）含量变化，并观察肺组织病理学变化。结果ALI组较假手术组肺组织PI3K、PKB mRNA表达及PKB磷酸化水平明显增强[PI3K mRNA（43．7±14．3）％vs（20．7±9．1）％，P〈0．05；PKB mRNA（52．2±22．2）％vs（22．2±10．2）％，P〈0．01；p-PKB／PKB0．547±0．036）vs（0．348±0．029），P〈0．05]，NF—κB活性变化同步增强（10．5±2．1vs2．4±0．5，P〈0．01），BALF中TNF-α、IL-1β高表达，且尤以注射LPS后表现更显著，差异有统计学意义（P〈0．05，P〈0．01）。ALI＋Wortmannin组PI3K、PKB mRNA及PKB酸化水平较ALI组和ALI＋LPS组明显下降[PI3K mRNA（31．3±8．5）％vs（43．7±14．3）％，（75．7±17．2）％，P〈0．05，P〈0．01；PKB mRNA（27．5±9．8）％vs（52．2±22．2）％，（69．7±14．3）％，P〈0．05，P〈0．01；p-PKB/PKB0．380±0．031）vs（0．547±0．036），（0．695±0．042），均P〈0．01）]，NF-κB活性、TNF—α及IL-1β含量也明显降低，差异有统计学意义（P〈0．05，P〈0．01）。结论PI3K／PKB号转导通路的活化参与了重症急性胰腺炎肺损伤的病理过程，PI3K／PKB号转导通路可被LPS激活并通过上调NF-κB活性、TNF-α及IL-1β水平而发挥作用。

英文摘要：

Objective To investigate the expression and significance of phosphtidylinositol 3- kinase/protein kinase B （PI3K/PKB） signal transduetion pathway in severe acute panereatitis-assoeiated lung injury. Methods Twenty-four healthy male Changhai pigs were randomized into four groups： sham operation group （ n = 6 ）, ALI group （ n = 6 ）, ALI plus LPS （ lipopolysaeeharide ） group （ n = 6 ） and ALI plus Wortmannin group （n =6）. The expression levels of PI3K and PKB were determined by both RT-PCR and Western blot. Activity changes of NF-κB were detected by eleetrophoretie mobility shift assay （EMSA）. Contents of TNF-α and IL-1β in bronehoaiveolar lavage fluid （BALF） were examined by ELISA. The histopathological changes of lung were observed. Results The expressions of mRNA and protein PI3K and PKB, NF-κB activity and TNF-α, IL-1β in BALF in ALI group were higher than those in sham operation group（P 〈 0. 05 or P 〈 0. 01 ）. In ALI plus LPS group, they increased significantly in comparison with ALI group and sham operation group after injection of LPS（P 〈 0. 05 or P 〈0.01 ）. In ALI plus Wortmannin group, these parameters were significantly inhibited by Wortmannin in comparisons with ALI group and ALI plus LPS group （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion The phosphtidylinositol 3-kinase/protein kinase B signal transduction pathway is found to participate in the pathological process of severe acute pancreatitisassociated lung injury through the up-regulations of NF-κB activity, TNF-α and IL-1β.