低剂量内毒素预处理保护内毒素介导的小鼠急性肝损伤及其机理探讨

山东大学学报(医学版)

低剂量内毒素预处理保护内毒素介导的
小鼠急性肝损伤及其机理探讨

耿嘉蔚¹，周薇²，范红¹，黄尤光³，邹成钢²，李树德³

(1. 云南省第一人民医院消化内科，昆明 650031; 2. 云南大学生物资源保护与利用重点实验室，昆明 650091；3. 昆明医学院生物化学教研室，昆明 650031)

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2009-02-16 发布日期:2009-02-16
通讯作者: 李树德

Pretreatment with lowdose lipopolysaccharide protects against acute liver injury induced by lipopolysaccharide in mice: A study of mechanism

GENG Jiawei¹, ZHOU Wei², FAN Hong¹, HUANG Youguang³，　ZOU Chenggang², LI Shude³

（1. Department of Gastroenterology, First People′s Hospital of Yunnan Province, Kunming 650031, China;
2. Laboratory for Conservation and Utilization of Bioresources, Yunnan University, Kunming 650091, China;
3. Department of Biochemistry, Kunming Medical College, Kunming 650031, China）

Received:1900-01-01 Revised:1900-01-01 Online:2009-02-16 Published:2009-02-16
Contact: LI Shude

摘要/Abstract

摘要： 目的研究低剂量内毒素(LPS)预处理对LPS介导的小鼠急性肝损伤的影响。方法LPS通过腹腔注射小鼠；丁基亚磺酰亚胺（BSO）处理耗尽小鼠肝脏谷胱苷肽(GSH)含量;血浆天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶（ALT）测定用全自动生化分析仪；基因表达测定采用RTPCR。结果① 低剂量LPS预处理降低高剂量LPS诱导的小鼠肝功能损伤；② 低剂量LPS刺激肝脏GSH含量升高；LPS预处理组GSH水平显著高于高剂量LPS处理组；③ BSO预处理后，LPS预处理组与高剂量LPS组的血浆ALT和AST水平没有差别；④ LPS处理导致转硫途径关键酶——胱硫醚β合酶活性以及GSH合成途径关键酶——γ谷氨酰半胱氨酸合成酶表达升高。结论低剂量LPS通过上调肝组织中GSH合成相关基因表达，增加GSH的含量，减轻高剂量LPS诱导的肝脏损伤。

关键词: 内毒素, 肝损伤, 谷胱苷肽, 胱硫醚β合酶, γ谷氨酰半胱氨酸合成酶, 小鼠

Abstract: To explore the effect of lowdose lipopolysaccharide (LPS) on acute liver injury induced by highdose lipopolysaccharide in mice. MethodsThe mouse model of acute liver injury was reproduced by intraperitoneal administration of LPS. GSH in the livers of mice was depleted by administering buthionine sulphoximine (BSO). Aspartate transaminase (AST) and alanine transaminase (ALT) in the plasma were measured by an automated biochemistry analyzer. The mRNA levels of cystathione (synthase (CBS) and γglutamylcysteine synthetase (GCS) were determined by RTPCR. Results① Pretreatment with lowdose LPS attenuated acute liver injury induced by highdose LPS in mice. ② Lowdose LPS treatment elicited hepatic glutathione (GSH) levels in mice. The levels of GSH in the group pretreated with lowdose LPS were higher than those in the group treated with highdose LPS. ③ Plasma levels of ALT and AST in the group pretreated with lowdose LPS were similar to those in the group treated with highdose LPS. ④ Lowdose LPS pretreatment resulted in an increase in CBS activity as well as GSC mRNA levels. ConclusionLowdose LPS attenuates acute liver injury induced by highdose LPS in mice by promoting hepatic GSH levels though upregulating activity or expression of GSH biosynthesisrelative genes.

Key words: Lipopolysaccharide, Liver injury, Glutathione, Cystathionine betasynthase, γGlutamylcysteine synthetase, mice

中图分类号:

耿嘉蔚1 ，周薇2 ，范红1 ，黄尤光3 ，邹成钢2 ，李树德3
. 低剂量内毒素预处理保护内毒素介导的
小鼠急性肝损伤及其机理探讨[J]. 山东大学学报(医学版), 2009, 47(02): 21-24.

GENG Jiawei¹, ZHOU Wei², FAN Hong¹, HUANG Youguang³，　ZOU Chenggang², LI Shude³
. Pretreatment with lowdose lipopolysaccharide protects against acute liver injury induced by lipopolysaccharide in mice: A study of mechanism[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(02): 21-24.

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