Department of Neonatal Surgery, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).
Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).
Med Sci Monit. 2019 Oct 31;25:8181-8189. doi: 10.12659/MSM.917380.
BACKGROUND This study aimed to investigate the effects of maresin-1 (MaR1) in a mouse model of caerulein-induced acute pancreatitis (AP). MATERIAL AND METHODS Fifty C57BL/6 mice with caerulein-induced AP were divided into the untreated control group (N=10), the untreated AP model group (N=10), the MaR1-treated (low-dose, 0.1 μg) AP model group (N=10), the MaR1-treated (middle-dose, 0.5 μg) AP model group (N=10), and the MaR1-treated (high-dose, 1 μg) AP model group (N=10). Enzyme-linked immunoassay (ELISA) measured serum levels of amylase, lipase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and IL-6 and mRNA was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA), protein carbonyls, superoxide dismutase (SOD), and the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) were measured. Histology of the pancreas included measurement of acinar cell apoptosis using the terminal-deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assay. Western blot measured Toll-like receptor 4 (TLR4), MyD88, and phospho-NF-kappaB p65, and apoptosis-associated proteins Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9. RESULTS Following treatment with MaR1, serum levels of amylase, lipase, TNF-alpha, IL-1ß, and IL-6 decreased, MDA and protein carbonyl levels decreased, SOD and the GSH/GSSG ratio increased in a dose-dependent manner. In the MaR1-treated AP mice, inflammation of the pancreas and the expression of inflammatory cytokines, pancreatic acinar cell apoptosis, Bcl-2 expression, and expression of TLR4, MyD88, and p-NF-kappaB p65 were reduced, but Bax, cleaved caspase-3, and cleaved caspase-9 expression increased. CONCLUSIONS In a mouse model of caerulein-induced AP, treatment with MaR1 reduced oxidative stress and inflammation and reduced apoptosis.
本研究旨在探讨maresin-1（MaR1）在鹅膏蕈碱诱导的急性胰腺炎（AP）小鼠模型中的作用。
50 只 C57BL/6 小鼠用鹅膏蕈碱诱导 AP，分为未治疗对照组（N=10）、未治疗 AP 模型组（N=10）、MaR1 低剂量（0.1μg）AP 模型组（N=10）、MaR1 中剂量（0.5μg）AP 模型组（N=10）和 MaR1 高剂量（1μg）AP 模型组（N=10）。酶联免疫吸附测定（ELISA）检测血清淀粉酶、脂肪酶、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平，逆转录定量聚合酶链反应（RT-qPCR）检测 mRNA。测量丙二醛（MDA）、蛋白羰基、超氧化物歧化酶（SOD）和还原型谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）的比值。胰腺组织学包括末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）测定法测量腺泡细胞凋亡。Western blot 测定 Toll 样受体 4（TLR4）、MyD88 和磷酸化核因子-κB p65，以及凋亡相关蛋白 Bcl-2、Bax、裂解 caspase-3 和裂解 caspase-9。
MaR1 治疗后，血清淀粉酶、脂肪酶、TNF-α、IL-1β和 IL-6 水平降低，MDA 和蛋白羰基水平降低，SOD 和 GSH/GSSG 比值呈剂量依赖性增加。在 MaR1 治疗的 AP 小鼠中，胰腺炎症和炎症细胞因子表达、胰腺腺泡细胞凋亡、Bcl-2 表达以及 TLR4、MyD88 和 p-NF-κB p65 的表达减少，但 Bax、裂解 caspase-3 和裂解 caspase-9 的表达增加。
在鹅膏蕈碱诱导的 AP 小鼠模型中，MaR1 治疗可减轻氧化应激和炎症反应，减少细胞凋亡。
