Department of Gastroenterology, Yuyao People's Hospital of Zhejiang Province, Yuyao, Zhejiang 315400, P.R. China.
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5934-5939. doi: 10.3892/mmr.2018.8614. Epub 2018 Feb 16.
The aim of the present study was to investigate the protective mechanism underlying of melatonin in severe acute pancreatitis (SAP). A total of 64 male Sprague‑Dawley rats were randomly divided into four groups: The sham operation (SO) group, SAP group, melatonin treatment (MLT) group and p38 inhibitor (SB203580) treatment (SB) group. Acute pancreatitis was induced by 5% taurocholate through retrograde infusion into the biliopancreatic ducts. The melatonin and SB203580 treatment groups were administered with MLT and SB 30 min before operation the induction of SAP. Rats in each group were euthanized at 6 and 12 h following SAP induction. Blood and pancreatic tissues were removed for inflammatory examination. Peripheral blood mononuclear cells (PBMCs) were isolated following sacrifice to measure the phosphorylation of p38 and nuclear factor‑κB (NF‑κB was measured as p65 and phosphorylation of p65). The pretreatment of melatonin significantly attenuated the severity of pancreatitis. In addition, melatonin also reduced serum amylase and proinflammatory cytokine levels, including tumor necrosis factor‑α, interleukin (IL)‑1 and IL‑6. The mean pathological scores for pancreatic tissues in the MLT group were higher than those for samples in the SO group, but were lower than those for samples in the SAP group at each time-point. Phosphorylation of p38 and p65 levels in the melatonin treatment group were lower than that in the SAP group, and higher in the SAP group than in the SO group, and the SB203580 treatment group. Furthermore, melatonin significantly inhibited the activation of p38 and NF‑κB in PBMCs. The authors revealed that melatonin may attenuate inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs. SAP is a severe disease with a high risk of morbidity and mortality. It is important to attenuated inflammatory reaction in acute pancreatitis. Thus, the authors studied melatonin, which is synthesized by the pineal gland and released into the blood. Previous studies have shown that melatonin serves a protective role in the early course of human acute pancreatitis, and melatonin concentration variations are closely related to the severity of acute pancreatitis. It may be concluded that melatonin may attenuates inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs.
本研究旨在探讨褪黑素在重症急性胰腺炎（SAP）中的保护机制。64 只雄性 Sprague-Dawley 大鼠随机分为四组：假手术（SO）组、SAP 组、褪黑素治疗（MLT）组和 p38 抑制剂（SB203580）治疗（SB）组。通过逆行输注牛磺胆酸钠至胆胰管诱导急性胰腺炎。褪黑素和 SB203580 治疗组在 SAP 诱导前 30 分钟给予 MLT 和 SB。每组大鼠在 SAP 诱导后 6 和 12 小时处死，取血和胰腺组织进行炎症检查。处死大鼠后分离外周血单个核细胞（PBMCs），以测量 p38 和核因子-κB 的磷酸化（p65 和磷酸化 p65 作为 NF-κB 测量）。褪黑素预处理可显著减轻胰腺炎的严重程度。此外，褪黑素还降低了血清淀粉酶和促炎细胞因子水平，包括肿瘤坏死因子-α、白细胞介素（IL）-1 和 IL-6。MLT 组的胰腺组织平均病理评分高于 SO 组，但低于 SAP 组。褪黑素治疗组的 p38 和 p65 磷酸化水平低于 SAP 组，高于 SO 组，SB203580 治疗组。此外，褪黑素可显著抑制 PBMC 中 p38 和 NF-κB 的激活。作者发现，褪黑素可能通过抑制急性胰腺炎大鼠和 PBMC 中 p38 MAPK 和 NF-κB 的激活来减轻炎症反应。SAP 是一种发病率和死亡率都很高的严重疾病。减轻急性胰腺炎中的炎症反应很重要。因此，作者研究了褪黑素，它是由松果体合成并释放到血液中的。先前的研究表明，褪黑素在人类急性胰腺炎的早期阶段发挥保护作用，并且褪黑素浓度的变化与急性胰腺炎的严重程度密切相关。综上所述，褪黑素可能通过抑制急性胰腺炎大鼠和 PBMC 中 p38 MAPK 和 NF-κB 的激活来减轻炎症反应。
