Liu Mingdong, Shi Liangliang, Zou Xiaoping, Zheng Xi, Zhang Feng, Ding Xiwei, Zhu Hao, Shen Yonghua
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Pancreatology. 2016 Sep-Oct;16(5):733-8. doi: 10.1016/j.pan.2016.06.002. Epub 2016 Jun 6.
BACKGROUND/OBJECTIVES: Pulmonary apoptosis is an important pathogenic mechanism of acute lung injury induced by many factors. This study aims to investigate whether the caspase inhibitor zVAD-fmk has a protective effect against lung injury in the severe acute pancreatitis model (SAP) in rats.
Seventy-two Sprague-Dawley rats were randomly divided into Sham, SAP, and SAP + zVAD-fmk groups. The SAP model was established by injection of 5% sodium taurocholate into the pancreatic duct. Animals were sacrificed at 3 h, 6 h, 12 h, and 24 h after operation and then HE staining analysis was performed to assess the lung injury. ELISA was used to detect the activity of myeloperoxidase (MPO) and the concentrations of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Western blotting was used to detect the expression of cleaved caspase-3 in the lung tissues.
Rats in SAP group showed obvious lung injury through pathologic examination. Pretreatment with zVAD-fmk significantly inhibited a post-SAP increase in the activation of MPO, TNF-α, IL-1β, and caspase-3, and decreased lung injury induced by SAP as determined by the pathologic score.
Our results suggest that apoptosis plays an important role in acute pancreatitis-associated lung injury (APALI), and inhibition of caspase activity may represent a new therapeutic approach for the treatment of APALI.
背景/目的：肺细胞凋亡是多种因素诱导急性肺损伤的重要致病机制。本研究旨在探讨半胱天冬酶抑制剂zVAD-fmk对大鼠重症急性胰腺炎模型（SAP）所致肺损伤是否具有保护作用。
将72只Sprague-Dawley大鼠随机分为假手术组、SAP组和SAP + zVAD-fmk组。通过向胰管内注射5%牛磺胆酸钠建立SAP模型。术后3小时、6小时、12小时和24小时处死动物，然后进行HE染色分析以评估肺损伤。采用ELISA法检测髓过氧化物酶（MPO）活性、肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）浓度。采用蛋白质免疫印迹法检测肺组织中裂解的半胱天冬酶-3的表达。
通过病理检查发现，SAP组大鼠出现明显的肺损伤。zVAD-fmk预处理显著抑制了SAP后MPO、TNF-α、IL-1β和半胱天冬酶-3激活的增加，并降低了由病理评分确定的SAP所致的肺损伤。
我们的结果表明，细胞凋亡在急性胰腺炎相关性肺损伤（APALI）中起重要作用，抑制半胱天冬酶活性可能代表一种治疗APALI的新方法。
