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阻塞性胆汁淤积大鼠肝脏胆固醇7α-羟化酶和核受体FXR、SHP表达变化
吴晓平,柴进,陈文生*
0
(第三军医大学西南医院全军消化病研究所,重庆 400038)
摘要:
目的:通过建立梗阻性黄疸动物模型,观察胆固醇7α-羟化酶(cholesterol 7alpha-hydroxylase,CYP7A1)、类法尼醇X受体(farnesoid X receptor,FXR)及小异源二聚体伴侣受体(small heterodimer partner,SHP)的表达变化,并分析CYP7A1和FXR、SHP之间的关系。方法:采用胆总管结扎术制备大鼠梗阻性黄疸模型,分别于术后1、3、14 d麻醉后放血处死。取大鼠肝脏,抽提总RNA,采用实时定量RT-PCR检测CYP7A1 mRNA表达;提取肝细胞核蛋白,采用蛋白质印迹技术检测FXR和SHP蛋白表达。结果:与假手术对照组相比,梗阻性黄疸组大鼠肝细胞CYP7A1 mRNA表达明显增强,FXR和SHP蛋白表达同步降低,差异均有统计学意义(P<0.001,P<0.05)。结论:CYP7A1表达增强可能与FXR、SHP表达减弱有关。
关键词:  胆固醇7α-羟化酶  类法尼醇X受体  小异源二聚体伴侣受体  阻塞性黄疸
DOI:10.3724/SP.J.1008.2009.01398
投稿时间:2009-06-22修订日期:2009-10-26
基金项目:国家自然科学基金(30570842).
Changes of cholesterol 7alpha-hydroxylase,farnesoid X receptor,and small heterodimer partner expression in liver tissues of rats with obstructive cholestasis
WU Xiao-ping,CHAI Jin,CHEN Wen-sheng*
(Institute of Gastrointestinal Diseases,Southwest Hospital,Third Military Medical University,Chongqing 400038,China)
Abstract:
Objective:To investigate the changes of cholesterol 7alpha-hydroxylase(CYP7A1),farnesoid X receptor(FXR),and small heterodimer partner (SHP) expression in liver tissues of bile duct ligated (BDL) rats,and to analyze the relationship between their expression.Methods: Obstructive cholestasis rat model was induced by bile duct ligation,and rats were sacrificed on day 1,3,and 14 after operation.The hepatic tissues were collected and the total mRNA was extracted.The CYP7A1 mRNA expression was determined by real-time RT-PCR.The protein expression of FXR and SHP in the nuclei was determined by Western blotting analysis.Results: Compared with sham-operated group,experimental obstructive cholestasis group had significantly enhanced CYP7A1 mRNA expression and decreased FXR,SHP expression(P<0.001,P<0.05).Conclusion: The up-regulation of CYP7A1 may be associated with the down-regulation of FXR and SHP.
Key words:  cholesterol 7alpha-hydroxylase  farnesoid X receptor  small heterodimer partner  obstructive jaundice