脂多糖诱导小鼠肝损伤模型及致死模型的建立  

Establishment of lipopolysaccharide inducing mouse acute liver injury and lethal model

作　　者：刘韦成[1] 罗学来[1] 李兆明[1] 邓豫[1] 曹小年[1] 杨熹[1] 李川[1] 金源[1] 李小兰[1] 陶德定[1] 胡俊波[1] 王晶[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院肿瘤研究所,武汉430030 [2]华中科技大学同济医学院免疫学系

出　　处：《中华实验外科杂志》2012年第2期330-332,F0004,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81072431、30872472、30973496、30800569）;华中科技大学自主创新基金（2010MS027）;国家973计划资助项目（2009CB521802）;中央高校基本科研业务费专项资金资助项目（2011JC062、2011JC063）

摘　　要：目的建立脂多糖（内毒素，LPS）单独诱导小鼠急性肝损伤模型及致死模型。方法分别以生理盐水、LPS10、30、50、80mg／kg腹腔注射小鼠，筛选LPS诱导小鼠急性肝损伤和致死剂量。分别以生理盐水、LPS30、50mg／kg腹腔注射小鼠，绘制各组小鼠的生存曲线，苏木素．伊红（HE）染色观察各组肝组织损伤情况，免疫组织化学染色检测肝组织核因子（NF）一KBp65蛋白的表达和核转位变化，酶联免疫吸附试验（ELISA）检测小鼠血清中肿瘤坏死因子（TNF）-α含量。结果对照组小鼠无死亡和肝组织损伤，肝组织内NF—KBp65蛋白表达水平低，无核转位现象，血清中TNF—oL含量低。腹腔注射LPS30mg／kg组小鼠无死亡，出现肝组织损伤，肝组织内NF．KBp65蛋白表达水平增加、出现核转位，血清中TNF—α含量升高，与对照组比较差异有统计学意义（P〈0．01）。腹腔注射LPS50mg／kg组小鼠存活不超过120h，肝组织严重损伤，肝组织内NF—icBp65蛋白表达水平以及核转位显著增加，血清中TNF-α含量显著增高，与对照组比较差异有统计学意义（P〈0．01）。结论成功建立脂多糖诱导肝损伤动物模型和致死模型，为在体内进一步研究p55PIK对LPS—NF—KB通路奠定基础。Objective To establish mouse acute liver injury model and lethal model induced by li- popolysaccharide （LPS） injection alone. Methods Mice were injected intraperitoneally （ i. p. ） with dif- ferent concentrations of LPS （0, 10, 30, 50, 80 mg/kg）. The physiological statuses of mice were ob- served. The liver tissue of mice was stained by Hematoxyhn and Eosin （HE） to examine the injury of the liver. The levels of tumor necrosis factor （TNF） -ct in mouse serum were detected by enzyme linked immu- nosorbent assay （ELISA）. The expression and nuclear translocation of nuclear factor （NF）-KB p65 in mouse liver tissue were measured by immunohistochemistry staining. Results No death and liver injury were found in control group mice. No increased NF-KB p65 protein expression and nuclear translocation in liver tissue and increased serum TNF-a levels were detected in control group mice. No deaths of mice were found in group with intraperitoneal injection of LPS at a concentration of 30 mg/kg. As compared with the control group, liver injury, increased NF-KB p65 protein expression and nuclear translocation in liver tissue and increased serum TNF-ct levels were detected in this group （ P 〈 0. 01 ）. Mice with intraperitoneal injec- tion of LPS at a concentration of LPS 50mg/kg survived no more than 120 h. As compared with the control group, liver injury, significantly increased NF-KB p65 protein expression and nuclear translocation in liver tissue and significantly increased serum TNF-ot levels were detected in this group （ P 〈 0. 01 ）. Conclusion Our research successfully establishes mice liver injury model and lethal model induced by LPS intraperito- neal injection alone, which provides stable research platform for further medical treatment.

关 键 词：急性肝损伤 模型 动物 脂多糖 

分 类 号：R285.5[医药卫生—中药学]