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首页> 外文期刊>Xenobiotica: the fate of foreign compounds in biological systems >Role of P-glycoprotein in restricting the brain penetration of tanshinone IIA, a major active constituent from the root of Salvia miltiorrhiza Bunge, across the blood-brain barrier.
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Role of P-glycoprotein in restricting the brain penetration of tanshinone IIA, a major active constituent from the root of Salvia miltiorrhiza Bunge, across the blood-brain barrier.

机译：P-糖蛋白在限制丹参酮IIA的脑部渗透中的作用，丹参酮IIA是丹参根中的主要活性成分，跨血脑屏障。

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Tanshinone IIA (TSA) is a major constituent of Salvia miltiorrhiza Bunge widely used in the treatment of stroke. This current study aimed to investigate the nature of brain penetration of TSA using several in vitro and in vivo models. The uptake and efflux of TSA in primary rat brain microvascular endothelial cells (RBMVECs) were altered in the presence of a PgP inhibitor or multidrug-resistance-associated protein (Mrp1/2) inhibitor. A polarized transport of TSA was found in RBMVEC monolayers with facilitated efflux from the abluminal to the luminal side. The polarized transport of TSA was attenuated by PgP or Mrp1/2 inhibitors. In an in situ rat brain perfusion model, TSA crossed the blood-brain barrier at a greater rate than that for sucrose, and the brain penetration was increased in the presence of a PgP or Mrp1/2 inhibitor. The brain levels of TSA were only about 31% of that in the plasma and it increased to 74-77% of plasma levels when verapamil or quinidine was coadministered in rats. The entry of TSA to the central nervous system (CNS) significantly increased in rats subjected to middle cerebral artery occlusion or treatment with quinolinic acid. The normalized brain penetration of TSA in mdr1a((-/-)) mice was much higher than the wild-type mice. Taken collectively, these findings provide evidence that TSA has limited brain penetration through the blood-brain barrier owing to the contribution of PgP and possibly Mrp1/2.
机译：丹参酮IIA（TSA）是丹参中的一种主要成分，广泛用于中风的治疗。这项当前的研究旨在使用几种体外和体内模型研究TSA的脑部渗透性质。在存在PgP抑制剂或多药耐药相关蛋白（Mrp1 / 2）抑制剂的情况下，原代大鼠脑微血管内皮细胞（RBMVEC）中TSA的摄取和流出发生了改变。在RBMVEC单层中发现了TSA的极化转运，其从腔外向腔外的流出很容易。 TSA的极化运输被PgP或Mrp1 / 2抑制剂减弱。在原位大鼠脑灌注模型中，TSA以比蔗糖更高的速率穿过血脑屏障，并且在存在PgP或Mrp1 / 2抑制剂的情况下，脑渗透增加。在大鼠中共同施用维拉帕米或奎尼丁后，脑中TSA的脑水平仅为血浆水平的31％，并增加至血浆水平的74-77％。在大脑中动脉闭塞或喹啉酸治疗的大鼠中，TSA进入中枢神经系统（CNS）的次数显着增加。 TSA在mdr1a（（-/-））小鼠中的正常脑渗透率远高于野生型小鼠。综上所述，这些发现提供了证据，表明由于PgP以及可能的Mrp1 / 2的贡献，TSA限制了大脑通过血脑屏障的渗透。

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