早期生长反应基因-1在大鼠急性胰腺炎合并肺损伤中的作用

Effects of early growth response factor 1 on lung injury complicating acute pancreatitis in rat

目的探讨早期生长反应基因-1(EGR-1)在急性胰腺炎(AP)合并肺损伤中的作用。方法将24只雄性Wistar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牛磺胆酸钠溶液,3h后处死动物,留取血清、胰腺及肺组织。检测血清TNF-α、IL-1β水平,进行胰腺组织病理评分,测定肺组织湿重/干重比,并对肺组织进行EGR-1免疫组化染色。另将原代培养的肺泡巨噬细胞(AM)分别采用不同浓度胰弹性蛋白酶进行刺激,通过免疫细胞化学染色检测EGR-1在AM的表达,并检测培养液中TNF-α、IL-1β的浓度。结果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TNF-α、IL-1β、胰腺组织病理评分及肺组织湿重/干重比均呈显著正相关,且表达细胞类型也有所不同。AM表达EGR-1程度与培养液TNF-比、IL-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合并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 effects of early growth response factor 1 （EGRF-1） on lung injury complicating acute pancreatitis in a rat model. Methods Twenty-four male Wistar rats were randomly divided into group A, B, C and D. Normal saline or sodium taurocholate solution in different concentrations was injected into common bile duct of group A, B, C and D, respectively. Three hours after injection animals were sacrificed, and blood, pancreas and lungs were harvested. Serum levels of TNF-α and IL-1β were determined. Pathologic scoring of pancreatitis was analyzed, and the wet/dry ratios of pulmonary weight were estinated too. The lung paraffin sections were immunohistochemically stained, observed and assayed semi-quantitatively. Primary cultured alveolar macrophages （AM） were randomly divided into 4 groups, and were stimulated with elastase solution in different concentrations for 2 hours. Immunocytochemical staining for EGRF-1 expression in AMs were observed and assayed semi-quantitatively, and the concentrations of TNF-α and IL-1β of culture media were determined too. Results Positive staining of EGRF-1 was more intense in pulmonary tissue in severer acute pancreatitis models. Furthermore, EGRF-1 staining sites were different among acute pancreatitis models with different severity. EGRF-1 expression in lungs was correlated with those parameters relevant to severity of pancreatitis and pulmonary injury. EGRF-1 expression in AM was correlated with TNF-α and IL-1β levels, and was partly dependant on ERK 1/2 pathway. Conclusion EGRF-1 may play an important role in lung injury during acute pancreatitis, and the possible mechanism relates to the release of inflammatory cytokines.