制备低剂量四氯化碳诱导小鼠慢性肝损伤模型的探讨
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2010年度北京市属高等学校人才强教深化计划中青年骨干人才(PHR201008390)。


Establishment of a mouse model of chronic hepatic injury induced by low dose carbon tetrachloride
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    目的 通过注射低剂量四氯化碳(carbon tetrachloride,CCl4)建立B/C小鼠肝损伤模型。方法 正常B/C小鼠随机分为正常对照组、油对照组、CCl4模型组。正常对照组常规饲养;油对照组腹腔注射鲁花花生油(10 μL/g,1次/3天,连续6周);CCl4模型组腹腔注射0.5% CCl4(10 μL/g,1次/3天,连续6周)。第6周,各组小鼠检测血清AST、ALT浓度,HE及Masson染色后观察小鼠肝脏结构、细胞形态及纤维化程度。结果 第6周CCl4模型组小鼠血清ALT(P=0.00)、AST(P=0.00)浓度极显著性增高,HE及Masson染色显示CCl4模型组小鼠肝上皮细胞呈广泛性空泡样变及大量坏死,肝小叶内出现明显的条索样纤维增生,其纤维化程度评分显著性升高(P =0.00),纤维显色积分光密度值极显著性增高(P =0.00)。结论 注射低剂量CCl4可以诱导B/C小鼠肝损伤模型,实验模型具备肝损伤和肝纤维化病理特征。

    Abstract:

    Objective The aim of this study was to establish a mouse model of chronic hepatic injury induced by low dose carbon tetrachloride (CCl4). Methods Twenty SPF male B/C mice (body weight 18-20 g) were randomly divided into three groups including the CCl4-treated group, oil-treated group and non-treated control group (n=5/group). Mice in the CCl4-treated group were intraperitoneally injected with 0.5% CCl4 prepared in oil. Mice in the oil group received intraperitoneal injection of oil. Mice in the non-treated control group were left untreated. After 6 weeks, the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, as well structure, cellular morphology and degree of fibrosis of the hepatic tissues were examined by histology with HE and Masson staining. Results After low dose CCL4 treatment, the serum ALT and AST were significantly increased(P =0.00). Histology with HE staining showed extensive vacuolar degeneration of hepatic epithelial cells and large number of necrotic foci. Histology with Masson staining revealed fibrous hyperplasia mainly located around hepatic lobules. Quantitative analysis of the fibrosis showed that the degree of fibrosis and the integrated optical density of fibrosis were significantly increased after CCl4 induction(P=0.00). Conclusion Low dose carbon tetrachloride can induce hepatic injury in B/C mouse models presenting pathological changes of hepatic injury and fibrosis.

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李梦,翟亚南,王晶晶,孟霞,孙泉,陈柏安,卢静.制备低剂量四氯化碳诱导小鼠慢性肝损伤模型的探讨[J].中国实验动物学报,2014,22(4):52~55.

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  • 收稿日期:2014-03-11
  • 最后修改日期:2014-02-19
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  • 在线发布日期: 2014-05-06
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