The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats
The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats
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DOI：
10.1213/ane.0000000000001171
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发表时间：
2016-05-01
影响因子：
5.7
通讯作者：
Gomez de Segura, Ignacio A.
中科院分区：
文献类型：
--
作者：
Ruiz-Perez, Daniel;Benito, Javier;Gomez de Segura, Ignacio A.
背景：超低剂量纳洛酮（一种阿片类药物和toll样受体4拮抗剂）可阻断瑞芬太尼诱导的痛觉过敏和相关的最低肺泡浓度（MAC）升高，但不能阻断耐受性。目的是确定toll样受体4拮抗剂伊布司特对大鼠MAC的影响，以及它如何预防瑞芬太尼的影响。方法：雄性Wistar大鼠随机分为5个治疗组（每组7只）：布司特腹腔注射10 mg/kg、瑞芬太尼静脉注射240 μ g/kg/h、瑞芬太尼加瑞芬太尼、瑞芬太尼加纳洛酮、生理盐水。每只大鼠每天（第0、2、4天）检测三次七氟醚MAC：基线（MAC- a），治疗后每隔1.5小时再检测两次MAC- b和MAC- c。结果：在第0天，布司特、瑞芬太尼、瑞芬太尼加布司特、瑞芬太尼加纳洛酮均能降低基线MAC (P < 0.01)，但生理盐水不能降低。在第2天和第4天也发现了类似的效果。在第0、2和4天发现对瑞芬太尼的耐受性，而布司特和纳洛酮都不能阻止这种耐受性。瑞芬太尼在第4天引起的MAC增加（P = 0.001）被布司特或纳洛酮阻止。结论：伊布司特除了降低MAC外，还能阻止瑞芬太尼引起的基线MAC延迟增加，但不能阻止瑞芬太尼耐受引起的MAC增加。
BACKGROUND: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil.METHODS: Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 mu g/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C).RESULTS: A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone.CONCLUSIONS: Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.