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清道夫受体A基因敲除对小鼠肝脏代谢及胆囊结石形成的影响

焦龙 何川琦 陈炳官 赵刚 蒋兆彦 胡海

同济大学学报(医学版)2017,Vol.38Issue(3):8-13,6.
同济大学学报(医学版)2017,Vol.38Issue(3):8-13,6.DOI:10.16118/j.1008-0392.2017.03.002

清道夫受体A基因敲除对小鼠肝脏代谢及胆囊结石形成的影响

Liver metabolism and cholesterol gallstone formation in SRA knockout mice with lithogenic diet

焦龙 1何川琦 1陈炳官 1赵刚 1蒋兆彦 1胡海1

作者信息

  • 1. 同济大学附属东方医院胆石病中心,上海 200120
  • 折叠

摘要

Abstract

Objective To investigate the role of scavenger receptor class A(SRA) gene in liver metabolism and cholesterol gallstone formation in mice with lithogenic diet.Methods Male SRA knockout (SRAKO) mice and male C57BL/6 mice were fed with lithogenic diet (containing 1.25% cholesterol and 0.5% cholic acid) or chow diet for 8 weeks.At the end of experiments animals were sacrificed, liver and gallbladder samples were collected.Macrophages in liver tissue were detected with immunofluorescence staining using F4/80 as marker;the protein level of SRA was determined by Western blot;the expression of genes involved in lipid metabolism and inflammation in liver tissue were detected by quantitative QT-PCR;free cholesterol and cholesteryl ester in liver tissue were assayed with enzymatic kits.Results Gallstone formed in all wild-type C57BL/6 and SRAKO mice, but none in the control group.Apparent lipid deposition and the infiltration of inflammation cells were observed in mice fed with LD diet.Hepatic SRA protein was increased in mice fed with LD diet.The mRNA expression of hepatic ABCG5, ABCG8 and IL-1, TNF-α were significantly elevated in C57BL/6 mice fed with LD diet compared to the control group ( P <0.05).In SRAKO mice fed with LD diet, the expression of hepatic ABCG8, ABCB4 and TNF-α mRNA were significantly higher than the control group ( P <0.05).Free cholesterol and cholesteryl ester significantly elevated in gallbladder of both wild-type C57BL/6 and SRAKO mice fed with LD diet compared to control group ( P <0.05).Conclusion The results showed that knockout of SRA gene could not prevent the formation of gallstone.High cholesterol may play a more critical role in the pathogenesis of gallstone formation.

关键词

胆固醇结石病/清道夫受体A/基因敲除/免疫/小鼠

Key words

cholesterol gallstone disease/scavenger receptor class A/knockout/immune/mice

分类

医药卫生

引用本文复制引用

焦龙,何川琦,陈炳官,赵刚,蒋兆彦,胡海..清道夫受体A基因敲除对小鼠肝脏代谢及胆囊结石形成的影响[J].同济大学学报(医学版),2017,38(3):8-13,6.

基金项目

国家自然科学基金(81670579) (81670579)

同济大学学报(医学版)

OACSTPCD

1008-0392

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