Changes of blood endocannabinoids during anaesthesia: a special case for fatty acid amide hydrolase inhibition by propofol?
Changes of blood endocannabinoids during anaesthesia: a special case for fatty acid amide hydrolase inhibition by propofol?
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DOI：
10.1111/j.1365-2125.2012.04175.x
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发表时间：
2012-07-01
影响因子：
3.4
通讯作者：
Engeli, Stefan
中科院分区：
文献类型：
--
作者：
Jarzimski, Carina;Karst, Matthias;Engeli, Stefan
目的我们研究的目的是更详细地描述不同麻醉方案中内源性大麻素的时间进程，并挑战异丙酚作为 FAAH 抑制剂的假设。 方法 在麻醉第一个小时内，对接受异丙酚全身麻醉的 14 名女性和 14 名男性以及接受硫喷妥钠/七氟烷的 14 名女性和 14 名男性进行麻醉期间内源性大麻素的测量。我们还用丙泊酚和已知的 FAAH 抑制剂 oloxa 离体培养全人血样本，并测定了 FAAH 酶动力学。结果 在丙泊酚和硫喷妥钠/七氟烷麻醉下，血浆 anandamide 类似地下降，并在 10 分钟后达到最低点。使用丙泊酚时，anandamide 的曲线下面积（平均值和 95% CI）为 53.3 (47.4, 59.2) nmol l-1 60 分钟，使用硫喷妥/七氟烷时为 48.5 (43.1, 53.8) nmol l-1 60 分钟 (P= NS)。阿那达酰胺和丙泊酚血浆浓度在任何时间点均不相关。异丙酚不抑制离体 FAAH 活性。重组人 FAAH 的酶动力学（平均值 +/- SD）为 Km= 16.9 +/- 8.8 mu mol l-1 和 Vmax= 44.6 +/- 15.8 nmol mg1 min-1 FAAH（无 50 mu mol 时），Km= 16.6 +/- 4.0 mu mol l-1 和 Vmax= 44.0 +/- 7.6 nmol mg1 min-1 FAAH l-1 丙泊酚（P= NS）。结论我们的研究结果挑战了丙泊酚麻醉和丙泊酚成瘾是由 FAAH 抑制直接介导的观点，但我们不能排除对大麻素受体的其他间接作用。
AIMSThe aim of our study was to describe the time course of endocannabinoids during different anaesthesia protocols in more detail, and to challenge the hypothesis that propofol acts as a FAAH inhibitor.METHODSEndocannabinoids were measured during the first hour of anaesthesia in 14 women and 14 men undergoing general anaesthesia with propofol and in 14 women and 14 men receiving thiopental/sevoflurane. We also incubated whole human blood samples ex vivo with propofol and the known FAAH inhibitor oloxa and determined FAAH enzyme kinetics.RESULTSPlasma anandamide decreased similarly with propofol and thiopental/sevoflurane anaesthesia, and reached a nadir after 10 min. Areas under the curve for anandamide (mean and 95% CI) were 53.3 (47.4, 59.2) nmol l-1 60 min with propofol and 48.5 (43.1, 53.8) nmol l-1 60 min with thiopental/sevoflurane (P= NS). Anandamide and propofol plasma concentrations were not correlated at any time point. Ex vivo FAAH activity was not inhibited by propofol. Enzyme kinetics (mean +/- SD) of recombinant human FAAH were Km= 16.9 +/- 8.8 mu mol l-1 and Vmax= 44.6 +/- 15.8 nmol mg1 min1 FAAH without, and Km= 16.6 +/- 4.0 mu mol l-1 and Vmax= 44.0 +/- 7.6 nmol mg1 min-1 FAAH with 50 mu mol l-1 propofol (P= NS for both).CONCLUSIONSOur findings challenge the idea that propofol anaesthesia and also propofol addiction are directly mediated by FAAH inhibition, but we cannot exclude other indirect actions on cannabinoid receptors.