[The role of oxidative inflammatory cascade on pancreatic fibrosis progression in mice induced by DBTC plus ethanol].

[The role of oxidative inflammatory cascade on pancreatic fibrosis progression in mice induced by DBTC plus ethanol].
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氧化炎症级联反应对 DBTC 加乙醇诱导小鼠胰腺纤维化进展的作用

DOI:
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发表时间:
2015
影响因子:
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通讯作者:
Hong Zhang
Hong Zhang
中科院分区:
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文献类型:
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作者:
Fang Liu;Shi Ying;Xiao;Xiao;Yu Chen;Hong Zhang

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客观化 目的探讨氧化炎性级联反应在二丁基二氯化锡(DBTC)加乙醇诱导的慢性胰腺炎(CP)小鼠胰腺纤维化进展中的作用及机制。 方法 将36只KM小鼠随机分为2组(n=18):对照组和模型组(DBTC+乙醇)。模型组小鼠尾静脉注射DBTC(8 mg/kg),饮用10%乙醇。造模2周、4周、8周后麻醉处死小鼠,HE、Masson染色观察胰腺病理变化及纤维化程度,免疫组织化学检测F4/80表达水平,测定胰腺组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化酶(MPO)含量。 结果 模型组2周时胰腺内可见明显的成纤维细胞和巨噬细胞(f4/80阳性染色)。术后4周和8周,巨噬细胞浸润明显增多,胰腺组织被纤维化组织的增生所替代。各时相点胰腺组织匀浆中超氧化物歧化酶降低,丙二醛和髓过氧化物酶活性显著升高。两组比较差异有统计学意义(P<0.05)。 结论 DBTC联合乙醇灌胃可成功建立小鼠慢性胰腺炎和胰腺纤维化模型。氧化炎性级联反应在胰腺纤维化的发生发展中起重要作用。
OBJECTIVE To explore the role and mechanism of oxidative inflammatory cascade in pancreatic fibrosis progression of chronic pancreatitis (CP) in mice induced by dibutyltin dichloride (DBTC) plus ethanol. METHODS Thirty-six KM mice were randomly divided into 2 groups (n = 18): control group and model group (DBTC combined with ethanol). The mice in model group were intravenously injected with DBTC (8 mg/kg) in tail vein and drink 10% ethanol. After modeling 2 weeks, 4 weeks and 8 weeks, the mice were anesthetized and sacrificed, the pathological changes and the degree of fibrosis in the pancreas were observed by HE and Masson staining, the F4/80 expression level were detected by immunohistochemistry, the content of superoxide dismutase (SOD), malondialdehyde(MDA) and myeloperoxidase (MPO) were measured in the pancreatic homogenates. RESULTS The fibroblasts and macrophages (f4/80 positive staining) could be seen obviously in pancreas of model group at 2 weeks. At 4 weeks and 8 weeks, macrophages infiltration increased and pancreatic tissue was substituted by the proliferation of fibrosis significantly. At every time-point, in pancreatic homogenates SOD was decreased, MDA and MPO markedly increased. There was significant differences between two groups (P < 0.05). CONCLUSION DBTC injection joint ethanol drinking can successfully establish the model of chronic pancreatitis and pancreatic fibrosis in mice. Oxidative inflammatory cascade plays an important role in the progression of pancreatic fibrosis.