Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats
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链脲佐菌素诱导的糖尿病大鼠 P-糖蛋白表达和功能的组织特异性改变

DOI:
10.1038/aps.2011.33
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发表时间:
2011-07
影响因子:
8.2
通讯作者:
Liu, Xiao-dong
Liu, Xiao-dong
中科院分区:
医学1区
文献类型:
--
作者:
Xie, Lin;Lu, Liang;Jin, Shi;Jing, Xin-yue;Yao, Dan;Hu, Nan;Liu, Li;Duan, Ru;Liu, Xiao-dong

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Aim:To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats.Methods:Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123.Results:In 5-and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues.Conclusion:Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.
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