Yoo Byung-Moo, Oh Tae-Young, Kim Young-Bae, Yeo Marie, Lee Jeong-Sang, Surh Young Joon, Ahn Byoung-Ok, Kim Wook-Hwan, Sohn Seonghyang, Kim Jin-Hong, Hahm Ki-Baik
Genome Research Center for Gastroenterology, Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Pancreatology. 2005;5(2-3):165-76. doi: 10.1159/000085268. Epub 2005 Apr 21.
BACKGROUND/AIM: Oxygen free radicals (OFRs) mediate an important step in the initiation of experimental acute pancreatitis and several clinical findings suggested the possible contribution of OFRs to the pathogenesis of pancreatic fibrosis. So far, there are no studies which reporting potential role of OFRs in development of chronic pancreatitis with the prevention with antioxidants. This study was aimed to establish the mice model of chronic fibrosing pancreatitis and to prove the involvement of OFRs in chronic pancreatitis with fibrosis.
Repeated intraperitoneal cerulein injection was performed to induce chronic pancreatitis in mice. Histological changes in the pancreas were examined, and markers for oxidative stress were measured in the pancreatic tissue and serum of the mice. DA-9601, a phytochemical possessing anti-inflammatory and antioxidative action, was given together with cerulein to the mice.
Repeated intraperitoneal injection of cerulein provoked significant severity of chronic fibrosing pancreatitis after 5 weeks. After treatment of DA-9601, the extents of pancreatic fibrosis were statistically significantly decreased in accordance with lessened pancreatic inflammations. The NF-kappaB binding activities were increased in chronic pancreatitis, which were significantly attenuated after DA-9601 treatment. The levels of myeloperoxidase and iNOS activities were also significantly decreased in DA-9601-treated group compared to the pancreatitis only group. Cytoprotective proteins such as heat shock protein-70 (HSP) and metallothionein were significantly increased in the DA-9601-treated group. DA-9601 decreased the expressions of alpha-SMA and type I collagen in cultured pancreatic stellate cells.
Oxidative stress was principally involved in the pathogenesis of chronic pancreatitis with fibrosis.
背景/目的：氧自由基（OFRs）在实验性急性胰腺炎的起始过程中介导了重要步骤，并且多项临床研究结果提示OFRs可能参与胰腺纤维化的发病机制。到目前为止，尚无研究报道OFRs在慢性胰腺炎发生发展及抗氧化剂预防作用中的潜在作用。本研究旨在建立慢性纤维化性胰腺炎小鼠模型，并证实OFRs参与伴有纤维化的慢性胰腺炎的发病过程。
通过反复腹腔注射雨蛙素诱导小鼠慢性胰腺炎。检查胰腺的组织学变化，并检测小鼠胰腺组织和血清中的氧化应激标志物。将具有抗炎和抗氧化作用的植物化学物质DA-9601与雨蛙素一起给予小鼠。
反复腹腔注射雨蛙素5周后引发了严重的慢性纤维化性胰腺炎。给予DA-9601治疗后，胰腺纤维化程度在统计学上显著降低，同时胰腺炎症减轻。慢性胰腺炎时核因子κB（NF-κB）结合活性增加，DA-9601治疗后显著减弱。与仅患胰腺炎的组相比，DA-9601治疗组的髓过氧化物酶水平和诱导型一氧化氮合酶（iNOS）活性也显著降低。DA-9601治疗组中细胞保护蛋白如热休克蛋白70（HSP）和金属硫蛋白显著增加。DA-9601降低了培养的胰腺星状细胞中α-平滑肌肌动蛋白（α-SMA）和I型胶原的表达。
氧化应激主要参与伴有纤维化的慢性胰腺炎的发病机制。
