早期生长反应基因-1与大鼠急性胰腺炎合并肺损伤

The role of early growth response factor 1 in lung injury complicated with rat acute pancreatitis.

目的通过观察早期生长反应基因-1(EGR-1)在AP大鼠肺组织和原代培养肺泡巨噬细胞(AM)中的表达及与TNF-αI、L-1β水平的关系,探讨EGR-1在AP肺损伤中的作用。方法将24只大鼠随机均分为4组,分别于胆管内逆行注入生理盐水或不同浓度的牛磺胆酸钠溶液。检测血清TNF-αI、L-1β水平,胰腺组织病理评分,肺组织湿重/干重比,并对肺组织进行EGR-1免疫组化染色。另将原代培养AM分成4组,分别采用不同浓度胰弹性蛋白酶进行刺激,检测EGR-1在AM的表达,并检测培养液中TNF-α、IL-β浓度。结果①肺组织免疫组化染色显示,EGR-1表达随AP病情加重而增强,并与反映AP病情及肺损伤各指标均呈显著正相关。②AM表达EGR-1程度与培养液TNF-αI、L-1β水平呈显著正相关,EGR-1在AM中的表达有ERK1/2信号途径的参与。结论EGR-1可能在AP并发肺损伤中起重要作用,其机制可能与其介导炎性细胞因子生成有关。

Objective To investigate the possible role of early growth response factor 1 （ EGR-1 ） in lung injury complicated with rat taurocholate sodium-lnduced acute pancreatitis.Methods （1）Twenty-four male Wistar rats were randomly divided into 4 groups,i.e. group A, B, C and D. Normal saline was injected into common bile duct（ CBD）of group A, and taurocholate sodium solutions with different concentrations were injected into CBD of group B, C and D. Three hours after injection all animals were sacrificed, and blood, pancreata and lungs were harvested. Serum levels of TNF-α and IL-1β were measured. Pathologic scoring of pancreas was analyzed, and pulmonary wet weight to dry weight ratios were measurd too. Immunohistochemical staining of EGR-1 on lung paraffin section was observed and assayed semi-quantltatlvely. （2）Primary cultured alveolar macrophages（AM ） were randomly divided into 4 groups, and were stimulated with elastase solution of different concentrations for 2 hours. Immunocytochemlcal staining of EGR-1 of AM was observed and assayed semiquantitatively, and the concentrations of TNF-α and IL-1β of cultured fluid were measured too. Results （1） Pulmonary positive staining of EGR-1 was more intense in severer acute pancreatitis models. EGR-1 expressed in lungs correlated with those parameters demonstrating pancreatitis severity and pulmonary injury.（2）EGR-1 expressed in AM correlated with TNF-α and IL-1β levels,and was partly dependant on ERK 1/2 pathway .Conclusion EGR-1 may play an important role in lung injury during acute pancreatltis,and the possible mechanism relates to its mediated production of inflammatory cytokines.