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四氯化碳诱导小鼠急性肝损伤模型的建立和优化
作者:朱安妮1 李蕊2 3 刘三海1 乔艳雪1 冯时2 3 苑少欣2 3 张剑平2 3 
单位:1.北京中医药大学基础医学院 硕士研究生 北京 100029 2.首都医科大学附属北京地坛医院 传染病研究所 北京 100015 3.新发突发传染病研究北京市重点实验室 北京 100015 
关键词:四氯化碳 急性肝损伤 C57BL/6小鼠 
分类号:
出版年,卷(期):页码:2014,6(1):27-31
摘要:

摘要:目的 通过单次腹腔注射不同剂量的四氯化碳(CCl4)致小鼠急性肝损伤,检测小鼠血浆转氨酶水平的变化,建立适合本研究的小鼠模型。方法 采用6~8周龄雄性C57BL/6小鼠单次腹腔注射CCl4诱导急性肝损伤。比较不同剂量的CCl4诱导急性肝损伤小鼠的血浆转氨酶水平。将182只小鼠随机分出32只。32只小鼠随机分为3组CCl4实验组(每组8只)和正常对照组(8只),分别腹腔注射0.1%、0.2%、0.3%的CCl4橄榄油溶液(10 ml/kg)或等体积橄榄油。注射12小时后取血,检测血浆丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的水平。比较0.1%和0.2%剂量组小鼠不同时间点血浆转氨酶水平的变化。将剩余150只小鼠随机分为正常对照组(10只)、实验Ⅰ组(0.1%剂量,70只)、实验Ⅱ组(0.2%剂量,70只),实验组小鼠在造模6、12、16、20、24、48、72小时后取血,检测血浆ALT、AST的水平。结果 与正常对照组相比,分别用0.1%、0.2%、0.3% CCl4处理后12小时小鼠血浆ALT、AST均明显升高(P < 0.05),并呈剂量依赖性。与正常对照组相比,0.1%和0.2%剂量组小鼠血浆ALT、AST的水平在早期均呈上升趋势,并分别在16小时和20小时达到高峰,随后逐渐下降,在72小时接近至正常水平。结论 单次腹腔注射CCl4诱导小鼠急性肝损伤呈剂量依赖性。0.1%剂量的CCl4以及该剂量处理后16小时是建立C57BL/6小鼠急性轻度肝损伤的合适剂量与检测转氨酶水平的合适时间点。

Abstract: Objective To establish an appropriate murine model for this study, the mice were administrated by single intraperitoneal injection at different doses with carbon tetrachloride (CCl4) to induce acute liver injury, and the changes of aminotransferase levels in plasma were measured. Methods Acute liver injury in C57BL/6 male mice (6-8 weeks) were administrated by single intraperitoneal injection with CCl4. Comparing the aminotransferase levels in plasma from different doses of CCl4-injected mice. The 32 mice were randomly separated from 182 mice. The 32 mice were randomly divided into normal control group (8 mice) and 0.1%, 0.2% and 0.3% CCl4 groups (8 mice per group) which received 0.1%, 0.2% and 0.3% CCl4 (10 ml/kg, dissolved in olive oil) respectively, while the normal control group received only olive oil as control. Twelve hours after challenge, the mice were sacrificed and plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Comparing the aminotransferase levels in plasma from 0.1% and 0.2% groups at different time points. The 150 mice were randomly divided into normal control group (8 mice), the experimental group Ⅰ (0.1% dose, 70 mice) and the experimental group Ⅱ (0.2% dose, 70 mice). Plasma levels of ALT and AST were measured at 6, 12, 16, 20, 24, 48 and 72 hours after challenge. Results Compared with normal control group, plasma ALT and AST were significantly increased (P < 0.05) in CCl4-treated mice at 12 hour, furthermore, the effect was dose-dependent in 0.1%, 0.2% and 0.3% groups. The levels of ALT and AST rised at the early phase in 0.1% and 0.2% groups, and reached the peak at 16 and 20 hours, respectively. Then the levels declined gradually and were close to the normal level at 72 hours. Conclusions The increase of ALT and AST levels was in a dose-dependent manner with CCl4 by single intraperitoneal injection. To establish acute mild liver injury in C57BL/6 mice, 0.1% of CCl4 was the appropriate dose, and 16 hours after challenge was the suitable time point for detection of aminotransferase levels.

基金项目:
北京市科技计划课题(No.Z111107056811044)
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