Effect Of PI3K Inhibitor Wortmannin On Pathogenesis Of Severe Acute Pancreatitis Associated With Acute Lung Injury.

Objective: To observe the influence of wortmannin to lung water ratio, lung pathologicaldamage, lung myeloperoxidase (myeloperocidase MPO), matrix metalloproteinase-9andphosphatidylinositol3kinase/protein kinase B (PI3K/PKB) signaling pathway expression inrats severe acute pancreatitis associated with acute lung injury,and to explore its mechanism..Methods: Fifty-six healthy adult male SD rats were randomly divided into the SO group,SAP group,SAP+W Group,cholangiopancreatography was retrograde uniform injected4%sodium taurocholate (0.1ml/100g)to make SAP-ALI model.SAP+W group were injectedWortmannin1.4mg/kg into intraperitoneal before modeling2-hour, SAP and SO group weregiven the same amount of modeling the same way corresponds to the solvent (saline),SO groupopen abdomenonly to flip the intestine and closed.SAP and SAP+W group detected the lungmoisture content, lung and pancreatic biopsy to observe lung and pancreatic pathologicaldamage; detected the protein kinase B (PKB) phosphorylation level to understand the activityof the PI3K signal transduction pathway; detected the lung tissue myeloperoxidase (MPO),matrix metalloproteinase-9(MMP-9) expression level of to understand the lung inflammatoryreaction at3h,6h and12h time points.Results: PKB expression rich in each group lung tissue of rats, but the expression of p-PKB aresignificantly different; SO group was lowest;in SAP group,p-PKB expression began to rise at3h after modeling, up to the highest at12h,compared with the SO group was significantlyincreased (P <0.05);in SAP+W group, p-PKB expression was also increasing gradually toreach its peak at12h,higher than SO group, but significantly lower than that in SAP group (P<0.05).In SAP group,MPO and MMP-9activity was gradually increased,the upward trend inline with the p-PKB, higher than SO group (P <0.05), and lung moisture content, pancreas andlung pathological damage also higher than the SO group (P <0.05); in SAP+W group, lungMPO and MMP-9upward trend also consistent with the p-PKB changes, but lower than SAPgroup (P <0.05), other indexs was lower than the SAP group (P <0.05).Conclusion:①MMP-9plays an important role in the process of PMN infiltrate to the lungtissue, the mechanism may be related to the effect of the decomposition cell basementmembrane with MMP-9, thereby increasing the PMN in the invasion and metastasis；②Excessive activation of the PI3K/PKB signal pathways that lead to expression of a large number of PMN activation and inflammatory factors (MMP-9), out of control resulting in lunginjury and further aggravated, indicating that this pathway plays an important role in thepathogenesis of SAP-ALI；③Wortmannin has a protective effect on lung injury with SAP,which may inhibit the PI3K pathway activity in neutrophils, reduce neutrophil activation,migration, and inhibition of inflammatory factors such as MMP-9and other related to therelease.