Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure
Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure
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DOI：
10.1016/s0014-2999(00)00699-3
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发表时间：
2000-10-20
影响因子：
5
通讯作者：
Takano, M
中科院分区：
文献类型：
--
作者：
Huang, ZH;Murakami, T;Takano, M
观察甘油诱导的大鼠急性肾功能衰竭对P-糖蛋白表达和功能的影响。在稳态血浆浓度下，通过测定P-糖蛋白底物罗丹明123(Rho-123)的肾分泌、胆汁清除率和脑分布来评价P-糖蛋白的体内功能。在急性肾功能衰竭大鼠中，肾脏中的P-糖蛋白水平增加了2.5倍，但肝脏和脑中的P-糖蛋白水平没有增加。相反，这些组织中的P-糖蛋白功能受到抑制。有趣的是，不仅Rho-123的肾脏清除率与肾小球滤过率相关，而且Rho-123的胆汁清除率也与肾小球滤过率相关。在Caco-2细胞中，肾衰大鼠血浆对P-糖蛋白介导的Rho-123转运的抑制作用大于对照组大鼠血浆。综上所述，急性肾功能衰竭患者的P-糖蛋白功能受到系统性抑制，即使P-糖蛋白水平保持不变或升高。这可能是由于某些内源性P-糖蛋白底物/调节剂在疾病状态下在血浆中积累所致。(C)2000 Elsevier Science B.V.保留所有权利。
The effect of glycerol-induced acute renal failure on P-glycoprotein expression and function was evaluated in rats. The in vivo function of P-glycoprotein was evaluated by measuring renal secretory and biliary clearance and brain distribution of rhodamine 123 (Rho-123), a P-glycoprotein substrate, under a steady-state plasma concentration. In acute renal failure rats, the P-glycoprotein level increased 2.5-fold in the kidney, but not in the liver and brain. In contrast, P-glycoprotein function in these tissues was suppressed. Interestingly, not only the renal but also the biliary clearance of Rho-123 was correlated with the glomerular filtration rate. In Caco-2 cells, plasma from renal failure rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of Rho-123 than did plasma from control rats. In conclusion, P-glycoprotein function was systemically suppressed in acute renal failure, even though the level of P-glycoprotein remained unchanged or rather increased. This may be due to the accumulation of some endogenous P-glycoprotein substrates/modulators in the plasma in disease states. (C) 2000 Elsevier Science B.V. All rights reserved.