Experimental Pathology Department, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain.
PCB Animal Facility-Parc Científic de Barcelona, Barcelona, 08028, Catalonia, Spain.
Int J Mol Sci. 2020 Jan 30;21(3):917. doi: 10.3390/ijms21030917.
Acute pancreatitis is an inflammatory disorder of the pancreas. Its presentation ranges from self-limiting disease to acute necrotizing pancreatitis (ANP) with multiorgan failure and a high mortality. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic, and water-soluble chemicals composed of repeating units of ethylene glycol. The present article explores the effect of PEG35 administration on reducing the severity of ANP and associated lung injury. ANP was induced by injection of 5% sodium taurocholate into the biliopancreatic duct. PEG35 was administered intravenously either prophylactically or therapeutically. Three hours after ANP induction, pancreas and lung tissue samples and blood were collected and ANP severity was assessed. To evaluate the inflammatory response, gene expression of pro-inflammatory cytokines and chemokine and the changes in the presence of myeloperoxidase and adhesion molecule levels were determined in both the pancreas and the lung. To evaluate cell death, lactate dehydrogenase (LDH) activity and apoptotic cleaved caspase-3 localization were determined in plasma and in both the pancreatic and lung tissue respectively. ANP-associated local and systemic inflammatory processes were reduced when PEG35 was administered prophylactically. PEG35 pre-treatment also protected against acute pancreatitis-associated cell death. Notably, the therapeutic administration of PEG35 significantly decreased associated lung injury, even when the pancreatic lesion was equivalent to that in the untreated ANP-induced group. Our results support a protective role of PEG35 against the ANP-associated inflammatory process and identify PEG35 as a promising tool for the treatment of the potentially lethal complications of the disease.
急性胰腺炎是一种胰腺炎症性疾病。其表现范围从自限性疾病到伴有多器官衰竭和高死亡率的急性坏死性胰腺炎（ANP）。聚乙二醇（PEGs）是非免疫原性、无毒且水溶性的化学物质，由乙二醇重复单元组成。本文探讨了 PEG35 给药对减轻 ANP 严重程度和相关肺损伤的影响。通过向胆胰管内注射 5%牛磺胆酸钠诱导 ANP。PEG35 分别预防性或治疗性静脉给药。在 ANP 诱导后 3 小时，收集胰腺和肺组织样本和血液，并评估 ANP 严重程度。为了评估炎症反应，在胰腺和肺中测定促炎细胞因子和趋化因子的基因表达以及髓过氧化物酶和粘附分子水平的变化。为了评估细胞死亡，在血浆以及胰腺和肺组织中分别测定乳酸脱氢酶（LDH）活性和凋亡裂解 caspase-3 的定位。当给予预防性 PEG35 时，可减轻与 ANP 相关的局部和全身炎症反应。PEG35 预处理还可防止与急性胰腺炎相关的细胞死亡。值得注意的是，即使胰腺病变与未治疗的 ANP 诱导组相当，PEG35 的治疗性给药也显著降低了相关的肺损伤。我们的结果支持 PEG35 对 ANP 相关炎症过程的保护作用，并将 PEG35 确定为治疗该疾病潜在致命并发症的有前途的工具。
