Lipopolysaccharide impairs blood-brain barrier P-glycoprotein function in mice through prostaglandin- and nitric oxide-independent pathways.
Lipopolysaccharide impairs blood-brain barrier P-glycoprotein function in mice through prostaglandin- and nitric oxide-independent pathways.
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DOI：
10.1007/s11481-008-9138-y
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发表时间：
2009-06
影响因子：
6.2
通讯作者：
Banks, William A.
中科院分区：
文献类型：
--
作者：
Salkeni, Mohamad A.;Lynch, Jessica L.;Otamis-Price, Tulin;Banks, William A.
P-糖蛋白（P-gp）是一种脑-血外排系统，控制许多药物和内源性物质进入脑的能力。体外研究表明，通过脂多糖（LPS）和肿瘤坏死因子-α介导的炎症状态首先损害，然后刺激P-gp活性。在这里，我们确定了LPS是否可以影响体内P-gp功能。用单次腹腔注射LPS（3 mg/kg）处理的小鼠显示出P-gp功能的抑制。通过脑灌注评估，抑制在LPS给药后18小时开始，并持续至给药后36小时。P-gp蛋白增加44%，与通过翻译后机制发生的P-gp抑制一致。与LPS对血脑屏障功能的其他影响不同，一氧化氮和前列腺素抑制都没有影响。我们的结论是，诱导的促炎状态，例如LPS治疗可以抑制P-gp功能在体内的血脑屏障。
P-glycoprotein (P-gp) is a brain-to-blood efflux system that controls the ability of many drugs and endogenous substances to access the brain. In vitro work has shown that inflammatory states mediated through lipopolysaccharide (LPS) and tumor necrosis factor-alpha first impair and then stimulate P-gp activity. Here, we determined whether LPS can affect P-gp function in vivo. Mice treated with a single intraperitoneal injection of LPS (3 mg/kg) showed an inhibition of P-gp function. As assessed by brain perfusion, inhibition began 18 h after LPS administration and lasted until 36 h after administration. P-gp protein was increased by 44%, consistent with P-gp inhibition occurring through post-translational mechanisms. Unlike other effects of LPS on blood–brain barrier function, neither nitric oxide nor prostaglandin inhibition had an effect. We conclude that induction of proinflammatory states as exemplified by LPS treatment can inhibit P-gp function in vivo at the blood–brain barrier.
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