喔漫青霉素抑制磷脂酰肌醇-3激酶／蛋白激酶B通路对大鼠重症急性胰腺炎急性肺损伤的影响  

Effect of phosphatidylinositol-3 kinase inhibitor Wortmannin on pathogenesis of severe acute pan- creatitis associated with acute lung injury

作　　者：鲍世韵 矫元君 毕建刚 沈艳 郭跃华 伍天崇[2] 

机构地区：[1]暨南大学第二临床医学院深圳市人民医院肝胆外科,深圳518020 [2]南方医科大学珠江医院肝胆一科

出　　处：《中华实验外科杂志》2012年第9期1777-1780,共4页Chinese Journal of Experimental Surgery

基　　金：深圳市科技计划资助项目（201102167）

摘　　要：目的探讨磷脂酰肌醇-3激酶（P13K）抑制剂喔漫青霉素（Wortmannin）在重症急性胰腺炎（SAP）肺损伤时对肺的保护作用及其作用机制。方法将健康成年雄sD大鼠56只随机分为假手术（SO）组、SAP组、SAP＋Wortmannin（SAP＋W）组，胰胆管逆行注入4％牛磺胆酸钠法建立SAP模型。动态检测肺含水率、髓过氧化物酶（MPO）、基质金属蛋白酶-9（MMP-9）、蛋白激酶B（PKB）、磷酸化蛋白激酶B（p-PKB）活性，观察胰腺、肺组织病理学变化。结果SAP组建模后3h肺组织p-PKB表达开始上升，至12h达最高，较s0组明显升高（582．95±34．72比191．344-39．53）（P〈0．05）；肺含水率、MPO、MMP-9活性也逐渐升高，肺损伤程度逐渐加重（P〈0．05）；SAP＋W组肺组织p-PKB表达3h后开始上升，至12h达最高，较SO组升高（455．65±40．47比191．34±39．53）（P〈0．05），但较SAP组明显降低（455．65±40．47比582．95±34．72）（P〈0．05），其余指标也较SAP组减轻。结论Wortmannin对SAP时肺损伤有一定保护作用，其机制可能与抑制了中性粒细胞内P13K通路活性，减少中性粒细胞活化、迁移，及抑制炎性因子如MMP-9等的释放有关。Objective To investigate the protective effect and mechanism of phosphatidylinositol-3 kinase （PI3K） inhibitor Wortmannin in severe acute pancreatitis （SAP） associated with acute lung injury. Methods Fifty-six rats were randomly divided into 3 groups： sham operation （SO） group （n =8）, SAP group （n =24）, and SAP ± Wortmannin （SAP ± W） group （n =24）. SAP model was induced by retro- grade injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water con- tent, myeloperoxidase （MPO）, matrix metalloproteinase-9 （MMP-9）, protein kinase B （PKB）, abd phosphorylatlon of protein kinase B （p-PKB） activity in the lung tissue were evaluated. Results In SAP group, the p-PKB expression in the lung tissue began to rise at 3 h after modeling, and reached the peak at 12 h （582.95 ± 34. 72 vs 191.34 ± 39.53 ） （P 〈 0.05 ） ; the rate of lung water content, MPO, and MMP- 9 activity were also gradually increased, and the degree of lung lesion gradually increased （ P 〈 0. 05 ） ; in SAP＋Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 b after modeling, reached the peak at 12 h, and higher than in SO group （455.65 ±40. 47 vs 191.34± 39.53 ） （ P 〈0. 05 ） , but significantly lower than that in SAP group （455.65 ± 40. 47 vs 582.95 ± 34. 72） （P 〈 0. 05 ）. The rest indicators in SAP ＋ Wortmannin group were also significantly decreased as compared with SAP group （P 〈 0. 05）. Conclusion Pretreatment with wortmannin could decrease the lung lesion of rats with SAP probably by inhibiting the activation of phosphatidylinositol 3-kinase signal transduction pathway in polymorphonuclear neutrophils （PMN） , reducing PMN activation and migration, further more, suppressing the release of MMP-9 and other inflammatory factors.

关 键 词：喔漫青霉素 磷脂酰肌醇-3激酶/蛋白激酶B 重症急性胰腺炎 急性肺损伤 

分 类 号：R657.51[医药卫生—外科学]