Role of cyclic adenosine monophosphate/protein kinase A signal transduction pathway in severe acute pancreatitis-associated lung injury

Abstract

Objective To investigate the mechanism of cyclic adenosine monophosphate / protein kinase A signal transduction pathway in severe acute pancreatitis(SAP)-associated lung injury.Methods Seventy-two male healthy SD rats were completely randomized into three groups:sham operation (SO) group(n =8),SAP group and SAP plus H89 (cAMP inhibitor) group,then the latter two groups were divided into four sub-groups with eight rats in each sub-group according to the sampling time of 3,6,12 and 24 h,and the total numbers of groups were nine.The content change of TNF-α and IL-1β in serum,protein levels of cAMP-dependent protein kinase catalytic subunit (PKA C) and phosphorylated vasodilator-stimulated phosphoprotein(p-VASP) and the expression of VSAP mRNA in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA),immunohistochemistry and quantitative real time PCR,respectively.Pathological changes of the pancreas and lung tissues were also observed.Results Compared with the SO group,the serum levels of TNF-α and IL-1β in the SAP group were obviously increased at different time points(P ＜0.05).Pathological changes of the pancreas and lung tissues were aggravated significantly.The protein levels of PKA C,p-VASP and the expression of VSAP mRNA in lung tissue were increased significantly (P ＜0.05)which peaked at 12 h in the SAP group [TNF-α was (266.07 ± 17.14) pg/mL,IL-1β(169.17 ±25.92) pg/mL,PKA C(210.69 ±6.32) × 103,p-VASP (56.62 ±0.57) × 103,VASP mRNA(2.06 ±0.21)],which had positive correlation with the serum level of TNF-α and IL-1β.Compared with the SAP group,pathological changes of the pancreas and lung tissues were alleviated significantly,the protein levels of PKA C,p-VASP and the expression of VSAP mRNA in lung tissue were decreased significantly in the SAP plus H89 group at different time points(P ＜ 0.05).Conclusion The cyclic adenosine monophosphate / protein kinase A signal transduction pathway is found to participate in the pathological process of SAP-associated lung injury through the up-regulations of TNF-α,IL-1 β and phospho-VASP. Key words: Pancreatitis; Cyclic AMP-dependent protein kinases; Lung injury; Vasodilator-stimulated phosphoprotein