西维来司钠对大鼠重症急性胰腺炎肺损伤的作用

摘要

目的 探讨西维来司钠(sivelestat sodium)对SD大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)肺损伤的作用及其可能机制.方法 健康成年SD大鼠24只随机分成3组:对照组、模型组、药物组,每组8只.逆行胰胆管注射5%牛磺胆酸钠建立SAP模型.药物组在模型基础上给予西维来司钠干预,对照组和模型组给予等量生理盐水.建模成功6h后处死大鼠,检测各组大鼠血清淀粉酶(AMS)、血清中性粒细胞弹性蛋白酶(NE)活性以及肺脏组织湿干比重(W/D)、髓过氧化物酶(MPO)活性、核因子-κB(NF-κB)活性,光镜下观察肺脏病理改变,并进行病理学评分.结果 与对照组比较,模型组肺组织MPO、NF-κB含量显著升高(P＜0.05),W/D比值显著升高(P＜0.05),血清AMS、NE显著升高(P＜0.05),光镜下可见肺组织出现明显的病理损伤(P＜0.05).与模型组相比,药物组的血清NE以及肺组织MPO、W/D、NF-κB含量显著降低(P＜0.05),但是AMS却没有显著降低(P>0.05).光镜下肺组织病理损害显著减轻(P＜0.05),其损伤程度介于对照组和模型组之间.结论 早期应用西维来司钠对减轻大鼠急性胰腺炎肺损伤程度具有一定的作用.其作用机制可能是:西维来司钠通过抑制NF-κB活性来抑制炎症反应,从而起到减轻重症急性胰腺炎肺损伤的作用.%Objective To explore the effect and its possible mechanism of sivelestat sodium on the lung injtuty of severe acute pancreatitis SD rats. Methods Twenty-four healthy SD rats were randomly divided into three groups: the control group, the severe acute pancreatitis grotup and the sirelesltat sodium treated group. SAP models were induced by retrograde injection of 5％ taurocholate sodium into the biliopancreatic duct of SD rats. In the drug group sivelestat sodium was given on the basis of SAP modei. While in the control group and the severe acute pancreatitis group, isometric physiological saline was given. Six hours later after the three groups of model were successfully established, serun neutrophil elastase (NE) activity was determined with the method of enzyme-linked imnunosobent assay (ELISA) in the venous. The sernm amylase (AMS) was determined with routine method. Wet to dry weight ratio (W/D) of lung and MPO in homogenate of harvested lung were assayed. Expression of NF-κB in pulmonic tissues was observed with immunohistochemistry (IHC). The pathologic change in pulmonic tissues were also measured. Results Compared with the control group, the concentration of MPO, NF-KB and W/D ratio of lung were significantly increased (P＜0.05) in the severe acute pancreatitis group, And the level of the serum NE was significantly increased (P＜0.05) in the severe acute pancreatitis group. The AMS was also significanlyincreased (P＜0.05) in the severe acute pancreatitis group. There were obviously histopathological injury of pulmonic tissues in the severe acute pancreatitis group (P＜0.05). Compared with the severe acute pancreatitis group, the concentration of MPO,NF-κB and lung W/D ratio were significantly descended (P＜0.05) in the sivelestat sodium treated group, and the level of serum NE was markedly lowered (P＜0.05). But the serum AMS was not significantty decreased (P＞0.05) itn the sivelestat sodium treated group. The pathological damage of pulmonary tissue in the sivelesttat sodium treated group was between the control group and the severe acute pancreatitis group. Conclusion The application of sivelestat sodium in earlier period can play definite role for the treatment of severe acute pancreatitis. Ifs possible mechanisms maybe that sivelestat sodium play a role of relieving severe acute lung injury by inhibiting the activity of NF-κB.