链脲佐菌素诱导糖尿病大鼠体内 P 糖蛋白表达和功能的组织特异性改变。
Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats.
机构信息
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
出版信息
Acta Pharmacol Sin. 2011 Jul;32(7):956-66. doi: 10.1038/aps.2011.33. Epub 2011 Jun 20.
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.
目的
研究链脲佐菌素诱导的糖尿病大鼠大脑皮质、海马、肝、肠黏膜和肾脏中 P 糖蛋白（P-GP）表达和功能的变化。
方法
通过单次链脲佐菌素（65mg/kg，ip）注射制备糖尿病大鼠。使用实时定量聚合酶链反应（QRT-PCR）分析和 Western blot 分别评估组织中 Abcb1/P-GP mRNA 和蛋白表达水平。通过测量 rhodamine 123 的组织-血浆浓度比和体液排泄百分比来研究 P-GP 功能。
结果
在 5 周和 8 周糖尿病大鼠中，大脑皮质和肠黏膜中 Abcb1a mRNA 水平显著降低，但海马和肾脏中显著升高。在肝脏中，5 周糖尿病大鼠中升高，8 周糖尿病大鼠中降低。Abcb1b mRNA 水平在大脑皮质、海马和肾脏中增加，但在肝脏和肠黏膜中降低。Western blot 结果与大多数检查组织中 Abcb1a mRNA 水平的变化一致。除肾脏组织外，大多数糖尿病大鼠组织中的 P-GP 活性明显降低。
结论
在糖尿病条件下，Abcb1/P-GP 的表达和功能的改变是组织特异性、Abcb1 特异性和糖尿病持续时间依赖性的。
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