大鼠重症急性胰腺炎肺泡巨噬细胞的活化和调控作用

The activation of rat alveolar macrophages in rats with severe acute pancreatitis

目的观察巨噬细胞中p38蛋白活化激酶对大鼠重症急性胰腺炎肺损伤的影响。方法假手术组仅胆胰管注射生理盐水0．1ml／100g；5％的牛黄胆酸（0．1ml／100g）逆行注射到SD大鼠的胆胰管内，造成重症急性胰腺炎（SAP）分为SAP组和SB03580组（SB203580，0．5mg／kg，静注）。在6h剖杀大鼠，查腹水，抽血检测血清淀粉酶（AMS）和肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6[酶联免疫吸附试验（ELISA）法]；同时分别离心收集全肺肺泡巨噬细胞，免疫组织化学检测肺组织及其巨噬细胞中p38 MAPK的表达，同时检测肺组织中的TNF-α和IL-6；光镜下检测胰腺组织损害。结果SAP组及SB组中AMS在6h分别为（4865．12±890．35）IU／L和（2918．24±614．58）IU／L，差异有统计学意义。血清TNF-α分别为（106．59±43．71）ng／L和（76．43±38．43）ng／L；IL-6是（2203．76±640．85）ng／L和（1254．76±459．35）ng／L，差异有统计学意义（P〈0．01）。肺组织中的TNF—α和IL-6的升高与血中的一致。光镜下，胰腺组织内可见炎细胞浸润、充血、水肿和坏死；在SAP组中肺组织及其巨噬细胞中p38 MAPK强烈表达，TNF-α和IL-6的表达一致，SB治疗组表达下降。结论TNF-α和IL-6在重症急性胰腺炎肺损伤起着重要作用；肺泡巨噬细胞中p38MAPK表达对TNF-α和IL-6的转录和合成起重要作用。

Objective To investigate the role of p38 protein kinase in the activation of rat alveolar macrophages （AMs） in rats with severe acute pancreatitis （SAP）. Methods Sixty Sprague Dawley rats were anesthetized, SAP was induced by low pressure retrograde infusion of biliopancreastic duct with 5% sodium taurocholate solution （0. 1 ml/100 g）, and the rats were divided into SAP group and SB203580 group （SB203580,0.5 mg/kg, i. v）. Thirty Sprague Dawley rats were injected with normal solution into biliopancreastic duct （0.1 mE/100 g）. Six h after operation, the rats were sacrificed. The serum and lung levels of TNF-α/IL-6 were determined by ELISA. The expression pattern of p38 MAPK in lung tissues and AMs was detected by immunohistochemistry. Results The levels of TNF-α/IL-6 and AMs in SAP group and SB group were increased more significantly than in sham-operated group （P 〈0.001 ）. The expression of p38MAPK in lung tissues and AMs was more significantly increased in SAP group and blocked by SB203580. Conclusion The serum levels of TNF-α/IL-6 in SAP rats were associated with severity of SAP. The induction of TNF-α and IL-6 in lung tissues and AMs may be mediated through the activation of p38 MAPK.