二硫代氨基甲酸吡咯烷在重症胰腺炎肺损伤中的作用

Role of pyrrolidine dithiocarbamate in lung injury of murine severe acute pancreatitis

目的 :观察二硫代氨基甲酸吡咯烷 (PDTC)对重症胰腺炎 (SAP)大鼠肺损伤的作用并探讨其机制。方法 :Wistar大鼠 4 0只 ,逆行胆胰管注射 5 %牛磺胆酸钠制备SAP模型。观察血清淀粉酶、动脉血氧分压 (PaO2 )、肺组织髓过氧化物酶 (MPO)活性、支气管肺泡灌洗液 (BALF)白蛋白含量 ;胰腺和肺组织病理变化及核因子 κB(NF κB)和诱导型一氧化氮合成酶 (iNOS)在肺组织中的表达。结果 :PDTC组较SAP组血清淀粉酶显著下降 ,PaO2 明显升高 ,胰腺、肺组织病理损伤减轻 ,BALF白蛋白含量 [PDTC组 (17.2 8± 2 .5 5 )mg/ml,(16 .5 3± 3.0 8)mg/ml;SAP组 (2 3.5 6± 0 .94 )mg/ml]和MPO活性 [PDTC组 (9.18± 1.70 )U/ g ,(8.6 9± 2 .0 6 )U/ g ;SAP组 (13.2 9± 3.36 )U/g]明显下降 ,同时肺组织NF κB和iNOS表达下调 ,P均 <0 .0 5。结论 :PDTC对SAP大鼠肺损伤有一定的治疗作用 ,其机制与其抑制NF κB活化、抑制中性粒细胞等多种炎性细胞的活化和调控iNOS基因的表达进而抑制一氧化氮的过量生成有关。

Objective: To investingate the role of pyrrolidine dithiocarbamate (PDTC) in the lung injury of murine severe acute pancreatitis (SAP) and the mechanisms.Methods:Rat SAP model was estabilished by retrograde injection of 5% sodium taurocholate into choledochopancreatic duct.The changes of serum amylase,patial pressure of arterial oxygen ( P aO_2),albumin content of bronchoalveolar lavage fluid,activity of myeloperoxidase(MPO),pancreas and lung morphological damage were observed. Expressions of nuclear factor-κB(NF-κB) and inducible nitric oxide synthetase(iNOS) in the lung were observed by using SP immunohistochemistry. Results:Compared with SAP group,in PDTC group level of serum amylase decreased significantly and level of P aO_2 improved. The pathological lesion of pancreas and lung were improved in PDTC group. The content of albumin in bronchoalveolar lavage fluid\[PDTC groups (17.28±2.55)and(16.53±3.08)mg/ml;SAP group (23.56± 0.94 )mg/ml,P< 0.05\] and MPO activity of lung tissue\[PDTC groups(9.18±1.70),( 8.69 ±2.06)U/g;SAP group(13.29±3.36)U/g,P< 0.05\] were obviously down regulated. The expressions of NF-κB and iNOS were obviously down regulated. Conclusion:The PDTC showed beneficial effects on lung injury in both functional and morphologic alterations during the course of SAP. The mechanisms are related with the inhibition of NF-κB activation,the activation of many kinds of inflammatory cells such as neutrophil and the genetic expression of iNOS.The iNOS induces the ultra-generation of nitric oxide which results in lung injury.