梗阻性黄疸患者十二指肠中乳腺癌耐药蛋白表达降低。
Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis.
作者信息
Zimmermann Christian, Hruz Petr, Gutmann Heike, Terracciano Luigi, Beuers Ulrich, Lehmann Frank, Beglinger Christoph, Drewe Juergen
机构信息
Department of Clinical Pharmacology, University Hospital of Basel, Basel, Switzerland.
出版信息
Digestion. 2006;74(2):101-8. doi: 10.1159/000097800. Epub 2006 Dec 7.
BACKGROUND/AIMS: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis.
METHODS
Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry.
RESULTS
We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%.
CONCLUSIONS
BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies.
背景/目的：在梗阻性胆汁淤积期间，参与胆汁酸稳态的转运蛋白的表达受到不同程度的调节。由于已知药物外排转运蛋白乳腺癌耐药蛋白（BCRP）可转运胆汁酸，我们研究了胆汁淤积期间十二指肠BCRP表达是否会发生改变。
方法
使用实时逆转录-聚合酶链反应（RT-PCR）分析，我们测定了19例胆汁淤积患者十二指肠组织中的mRNA表达水平。将表达水平与14名健康受试者进行比较。通过免疫组织化学法测定6例胆汁淤积患者和6名健康受试者活检组织中的BCRP蛋白染色情况。
结果
我们发现，梗阻性胆汁淤积患者的十二指肠BCRP mRNA平均水平显著降低至53%，平均蛋白染色降低至57%。
结论
BCRP是一种胆汁酸和多种药物的转运蛋白，在胆汁淤积期间，其在人十二指肠中的表达似乎下调。这些结果的临床影响有待进一步研究探讨。
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