Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats
Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats
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DOI：
10.1016/j.jphs.2018.08.006
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Yokoyama, Masataka
中科院分区：
文献类型：
--
作者：
Locatelli, Fabricio M.;Kawano, Takashi;Yokoyama, Masataka
老年小胶质细胞对手术的不适应反应和随之而来的神经炎症是术后认知功能障碍（POCD）的关键致病因素。在此，我们评估了白藜芦醇（RESV）对老年大鼠POCD的预防作用。选择RESV的乳化形式（e-RESV）以提高其口服和脑生物利用度。动物被分配到四组中的一组：e-RESV （80 mg/kg）、腹部手术载体治疗和单独异氟醚麻醉（每组n = 8）。e-RESV在0 ~ 60 mg/kg剂量范围内的剂量依赖性效应也被评估。术前24小时ig给药载体或e-RESV。手术后7天，使用一种新的物体识别测试评估认知功能，随后测量海马促炎细胞因子水平。我们的研究结果显示，在40 mg/kg或更高剂量下，e-RESV预处理可以减轻手术引起的认知障碍和相关的海马神经炎症。此外，离体实验显示，先发制人的e-RESV方案降低了海马小胶质细胞对脂多糖的免疫反应性。此外，e-RESV诱导的神经保护作用被同时给药sirtinol（一种特异性SIRT1抑制剂）所抑制。我们的研究结果表明，e-RESV通过SIRT1信号通路预防POCD的潜力。(c) 2018年作者。由Elsevier B.V.代表日本药理学会制作和主办。
The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.