核因子-κB激活与细胞凋亡在重症急性胰腺炎肺损伤中的作用

Role of nuclear factor-κB activation and cell apoptosis in severe pancreatitis-associated lung injury

目的：探讨重症急性胰腺炎（SAP）大鼠肺组织中核因子-κB（NF-κB）活化及细胞凋亡与肺损伤的关系.方法：SD大鼠随机分为对照组、SAP组、二硫代氨基甲酸吡咯烷（PDTC）预处理组.建立各组模型后取肺组织行光镜和电镜下病理观察,免疫组织化学观察NF-κB的表达,TUNEL法观察细胞凋亡情况.结果：对照组细胞结构基本正常,仅极少量NF-κB活化,且只有少量肺泡间质细胞和肺泡上皮细胞凋亡.SAP组可见Ⅱ型肺泡上皮细胞及血管内皮细胞有线粒体肿胀、基膜增宽、核染色质边集、间质水肿、电子密度升高等病理改变.NF-κB表达及细胞凋亡指数均明显升高,并呈动态变化,6h达高峰,NF-κB表达及凋亡细胞主要见于中性粒细胞、单核/巨噬细胞、支气管黏膜上皮细胞、肺泡上皮细胞及部分血管内皮细胞.PDTC预处理组病理改变减轻,NF-κB表达及细胞凋亡指数均明显下降,但仍高于对照组.结论：SAP时肺组织NF-κB活化并通过诱导细胞凋亡参与肺损伤.PDTC可能通过抑制NF-κB活性及细胞凋亡,对肺损伤具有保护作用.

Objective： To explore the relationship between intrapulmonary activition of nuclear factor-κB （NF-κB）, cell apoptosis and pulmonary injury in rats with severe acute pancreatitis （SAP）. Methods： SD rats were randomly divided into control group, SAP group and PDTC pretreated group. SAP was induced by retrograde injection of 5 % sodium taurocholate into the bile-pancreatic duct （0. 1 ml/100 g）. Histological changes of the lungs were observed after hematoxylin-eosin （HE） staining. Activation of NF-κB in the pulmonary tissues was detected by immunohistochemical methods. The cell apoptosis in the pulmonary tissues was observed by using TUNEL method. Results： A little positive signals were observed and a small number of apoptosis cells were seen in the epithelial and interstitial cells of the lung alveolus in the control group. The structure of ceils was basically normal. In type II alveolar epithelial cells and vascular endothelial cells, mitochondria swelling appeared in all SAP groups, the basement membrane widened, the nuclear chromatin aggregated to border, interstitial edema and the electron density increased. The expression of NF-κB and apoptosis index significantly increased and exhibited changes, and reached its peak at 6h. The positive signals and apoptotic cells were mostly observed in the neutrophils, macrophages, bronchial epithelial cells, alveolar epthelial cells and partial mierovascular endothelium cells. The PDTC pretreated groups showed a decrease in pathological changes. The expression levels of NF-κB and apoptosis index were significantly weaker than those in the SAP groups, but still significantly higher than those in the control group. Conclusion： The activation of NF-xB may be involved in the SAP lung injury through inducing apoptosis. PDTC might inhibit the activation of NF-xB and apoptosis and then effectively alleviate severity of lung injury.