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首页> 外文期刊>RSC Advances >Cytosolic -glucosidase inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of salidroside in hypoxic rats
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Cytosolic -glucosidase inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of salidroside in hypoxic rats

机译：细胞溶胶 - 葡糖苷酶抑制和肾血流抑制是缺氧大鼠中Salidroside的增强系统暴露的原因

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摘要

The promising benefits of salidroside (SAL) in alleviating high altitude sickness boost investigations on its pharmacokinetics and biological activity. However, the transportation and disposition process of SAL under hypoxic conditions has never been explored. The current study was proposed to investigate the pharmacokinetics of SAL in hypoxic rats and to explore the underlying mechanisms for the distinct metabolic fate of SAL under hypoxia. Pharmacokinetic studies on SAL was conducted in both hypoxic and normoxic rats. The transport properties of SAL were investigated on both hypoxic and normoxic Caco-2 monolayer models. Enzymes involved in SAL metabolism were identified and the effects of hypoxia on these enzymes were assessed by real-time PCR, western blotting analyses, and rat liver homogenate incubation. The renal clearance (CLr) of SAL, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in both hypoxic and normoxic rats were also determined for renal function assessment. It was found that the systemic exposure of SAL in hypoxic rats was remarkably higher than that in normoxic rats. The barrier function of Caco-2 monolayer was weakened under hypoxia due to the impaired brush border microvilli and decreased expression of tight junction protein. Hepatic metabolism of SAL in hypoxic rats was attenuated due to the reduced activity of cytosolic -glucosidase (CBG). Moreover, CLr of SAL was reduced in hypoxic rats due to the suppressed ERPF. Our findings suggest the potential need for dose-adjustment of SAL or its structural analogs under hypoxic conditions.
机译：Salidroside（SAL）减轻高海拔疾病的有前途的益处提高了其药代动力学和生物活性的研究。然而，从未探索过缺氧条件下SAL的运输和处置过程。提出了目前的研究，以研究缺氧大鼠中SAL的药代动力学，并探讨缺氧下SAL不同代谢命运的潜在机制。对脱氧和常氧的大鼠进行了药代动力学研究。研究了SAL的运输性质，对缺氧和常氧的Caco-2单层模型进行了研究。鉴定了涉及SAL代谢的酶，并通过实时PCR，Western印迹分析和大鼠肝均匀孵育来评估缺氧对这些酶的影响。还测定了肾功能评估的肾功能和常氧大鼠中Sal，有效肾脏等离子体流（ERPF）和肾小球过滤速率（GFR）的肾间隙（CLR）。结果发现，缺氧大鼠中SAL的全身暴露显着高于常氧大鼠。由于刷边框薄膜损害，CaCO-2单层的阻隔功能在缺氧下削弱了缺氧，并且紧缩结蛋白的表达减少。由于细胞溶胶 - 葡糖苷酶（CBG）的活性降低，缺氧大鼠中SAL的肝脏代谢被衰减。此外，由于抑制的ERPF，缺氧大鼠的SAL的CLR降低。我们的研究结果表明，在缺氧条件下潜在地调整SAL或其结构性类似物的需求。

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  • 来源
    《RSC Advances》 |2018年第16期|共15页
  • 作者

    Qi Te; Ge Bei-kang; Zhao Liang; Ma Yi; Li Xiao-rong; Xu Ping-xiang; Xue Ming;

  • 作者单位

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

    Capital Med Univ Beijing Lab Biomed Detect Technol &

    Instrument Dept Pharmacol Sch Basic Med Sci Beijing Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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