CCl_4和脂多糖诱导的急性肝损伤中肝细胞凋亡病理特点比较  

Comparison of Hepatocyte Apoptosis Induced by CCl_4 and LPS in Mice

作　　者：周滔[1] 闫秀川[1] 杨珂[1] 陶艳艳[1] 刘成海[1] 

机构地区：[1]上海中医药大学附属曙光医院上海中医药大学肝病研究所,上海201203

出　　处：《中国实验动物学报》2007年第5期347-350,I0001,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：教育部新世纪优秀人才资助计划(NCET-04-0437);上海市科委重点基础项目(04JC14069);上海市教育委员会E-研究院建设计划(E03008);上海市重点学科建设项目(Y0302)

摘　　要：目的比较CCl4和脂多糖诱导的两种急性肝损伤模型中肝细胞凋亡的病理特点。方法雄性BABL/c小鼠随机分为正常组、CCl4模型组与脂多糖模型组。CCl4和脂多糖模型小鼠分别腹腔注射0.03 mL/kg 50%CCl4/橄榄油混合液和10μg/kg脂多糖与900μg/kg半乳糖胺。9 h后采集标本,检测肝细胞凋亡,血清ALT、AST活性,肝组织SOD活性、MDA含量。结果与正常组比较,CCl4和脂多糖模型小鼠血清ALT与AST活性均明显升高(P<0.01),且脂多糖模型高于CCl4模型(P<0.01);模型小鼠均有明显肝细胞凋亡(P<0.01),且两组间无显著差异,但CCl4模型呈局灶性,以中央静脉周围为主;脂多糖模型呈弥漫性,肝细胞坏死与肝组织炎症更显著(P<0.01)。CCl4和脂多糖模型肝组织均SOD活性升高、而MDA含量下降(P<0.01),但CCl4模型更显著(P<0.05)。结论CCl4与脂多糖诱导的急性肝损伤小鼠模型均有明显的肝细胞凋亡,但CCl4模型以中央静脉区为主,脂质过氧化损伤更为明显;脂多糖模型呈弥漫性,肝细胞坏死与肝组织炎性反应较重。Objective To study hepatocyte apoptosis induced by CCl4 and LPS in mice. Methods 24 male BABL/c mice were randomly divided into 3 groups： normal group （8）, CCl4 model group （8） and LPS model group （8）. The mice of CCl4 model group received intraperitoneal injection of 50% CCl4 （0.03 mL/kg）, while the mice of LPS group were intraperitoneally injected with LPS （10 μg/kg） and galactosamine （900 μg/kg）. All the mice were sacrificed at 9 h after injection. The serum parameters of liver function （ALT, AST） were determined with assay kits. Hepatocyte necrosis was examined with HE staining and hepatocyte apoptosis with TUNEL. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity were measured with corresponding kits. Results Compared to normal mice, the two experimental models had higher levels of serum ALT and AST （ P 〈 0.01 ）, but the LPS model showed even higher levels of serum ALT and AST than those in CCl4 model group （ P 〈 0.01 ）. HE staining showed significant necrosis of hepatocytes and infiltrating inflammatory cells in the liver in both model groups. The necrotic hepatocytes and infiltrating inflammatory cells were limited and mainly around central veins in hepatic lobules in mice of CCl4 models, but dispersed in LPS models. There were more necrotic hepatocytes in the mice of CCl4 group than in LPS group （ P 〈 0.01）. TUNEL staining showed many apoptotic hepatocytes in liver in both models, and its distribution is similar to that of necrosis and inflammation. The apoptotic index of hepatocytes in mice of the two model groups was not significantly different （ P 〉 0.01 ）. Compared to normal mice, the liver in mice of two models had higher level of SOD, but lower level of MDA （ P 〈 0.01 ）, and the changes of SOD and MDA in liver of mice of CCl4 model group were more significant than those of LPS model group （ P 〈 0.05）. Conclusion Obvious apoptosis of hepatocytes can be induced by CCl4 and LPS in mice, accompanied by hepatic

关 键 词：细胞凋亡 坏死 脂质过氧化作用 脂多糖类 四氯化碳 

分 类 号：R575.1[医药卫生—消化系统] R361.2[医药卫生—内科学]