Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
复制标题
Resolvin D1 可预防实验性急性胰腺炎和相关肺损伤中的炎症
DOI：
10.1152/ajpgi.00355.2014
复制
发表时间：
2016-03-01
影响因子：
4.5
通讯作者：
Zhou, Zong-Guang
中科院分区：
文献类型：
--
作者：
Liu, Yong;Zhou, Dan;Zhou, Zong-Guang
急性胰腺炎是一种炎症性疾病，可导致多系统器官衰竭，死亡率相当高。近年来，消退素D1（Resolvin D1，RvD1）作为一种内源性抗炎脂质介质已被证实对许多炎症性疾病具有保护作用。本研究旨在探讨RvD1在急性胰腺炎及其相关肺损伤中的作用。分别用雨蛙肽或雨蛙肽与LPS联合诱导大鼠急性胰腺炎。在第一次注射雨蛙肽之前30分钟，用RvD1以300 ng/小鼠的剂量预处理小鼠。AP的严重程度通过生化标志物和组织学来评估。测定胰腺和肺组织中细胞因子和髓过氧化物酶（MPO）水平，以评估炎症反应的程度。通过蛋白质印迹法测定NF-κ B活化。蛙皮素或蛙皮素与LPS的联合注射导致胰腺局部损伤和相应的全身炎症变化，在蛙皮素和LPS组中具有显著的严重性。预处理的RvD1显著降低了淀粉酶、脂肪酶、TNF-α和IL-6血清水平的程度;胰腺和肺中的MPO活性;胰腺NF-κ B活化;以及胰腺损伤和相关肺损伤的严重程度，特别是在重症急性胰腺炎模型中。提示RvD 1可通过抑制NF-κ B B的活化，改善胰腺和肺的损伤，发挥抗炎作用，对重症急性胰腺炎的保护作用更为显著。这些发现表明，RvD1可能构成一种新的治疗策略，在重症急性胰腺炎的管理。
Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.