Department of Physiology and Pharmacology, IBSAL (Instituto Biosanitario Salamanca), University of Salamanca, 37007 Salamanca, Spain.
Pulm Pharmacol Ther. 2012 Aug;25(4):319-24. doi: 10.1016/j.pupt.2012.05.009. Epub 2012 Jun 9.
Pulmonary complications are frequent in the course of acute pancreatitis. We investigate the effects of dexamethasone on lung injury in mild and severe AP. Mild and severe acute pancreatitis was induced in rats by bile-pancreatic duct obstruction and infusion of 3.5% sodium taurocholate into the bile-pancreatic duct, respectively. Dexamethasone (1 mg/kg) was given by intramuscular injection 1 h after acute pancreatitis. Plasma amylase activity was measured to evaluate the pancreas damage. Lungs were harvested for analysing mRNA expression of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity (as index of neutrophil infiltration) and histological examination. Dexamethasone reduced the hyperamylasemia and hindered the pulmonary upregulation of MCP-1, CINC, P-selectin and ICAM-1, in both mild and severe acute pancreatitis. Despite this, dexamethasone treatment failed to reduce MPO activity and histological alterations developed in lungs during acute pancreatitis, either in bile-pancreatic duct obstruction or sodium taurocholate model. We conclude that pulmonary local factors different from inflammatory mediators contribute to leukocyte recruitment, so that although dexamethasone down-regulated the lung expression of chemokines and adhesion molecules during acute pancreatitis it was not able to prevent leukocyte infiltration, which could be responsible for maintaining the lung injury in either mild or severe acute pancreatitis.
在急性胰腺炎的病程中,肺部并发症很常见。我们研究了地塞米松对轻症和重症急性胰腺炎肺损伤的影响。通过胆管-胰管阻塞和向胆管-胰管内输注 3.5%牛磺胆酸钠分别在大鼠中诱导轻症和重症急性胰腺炎。在急性胰腺炎后 1 小时通过肌肉内注射给予地塞米松(1mg/kg)。测定血浆淀粉酶活性以评估胰腺损伤。收获肺组织以分析单核细胞趋化蛋白-1(MCP-1)、细胞因子诱导的中性粒细胞趋化因子(CINC)、P-选择素和细胞间黏附分子-1(ICAM-1)的 mRNA 表达、髓过氧化物酶(MPO)活性(作为中性粒细胞浸润的指标)和组织学检查。地塞米松降低了高淀粉酶血症,并抑制了轻症和重症急性胰腺炎中肺组织 MCP-1、CINC、P-选择素和 ICAM-1 的上调。尽管如此,地塞米松治疗未能降低 MPO 活性,并且在胆管-胰管阻塞或牛磺胆酸钠模型中,急性胰腺炎期间肺组织发生了组织学改变。我们得出结论,与炎症介质不同的肺部局部因素有助于白细胞募集,因此,尽管地塞米松在急性胰腺炎期间下调了趋化因子和黏附分子在肺中的表达,但它不能防止白细胞浸润,这可能是维持轻症或重症急性胰腺炎中肺损伤的原因。