Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain
Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain
复制标题
DOI：
10.1097/01.anes.0000264762.48920.80
复制
发表时间：
2007-04-01
期刊：
影响因子：
8.8
通讯作者：
Maze, Mervyn
中科院分区：
文献类型：
--
作者：
Ma, Daqing;Williamson, Peter;Maze, Mervyn
背景资料：麻醉剂，包括异氟烷和一氧化二氮，一种谷氨酸受体的N-甲基-D-天冬氨酸亚型的拮抗剂，已被证明在神经发育期间给药时可诱导凋亡性神经变性。氙也是一种N-甲基-D-天冬氨酸拮抗剂，不仅缺乏其他N-甲基-D-天冬氨酸拮抗剂产生的特征毒性，而且还减弱了这类药物产生的神经毒性。因此，目前的研究试图探讨氙对麻醉诱导的神经元凋亡的假定保护特性。（每组n = 5或6只）7日龄大鼠随机分配并暴露于8种气体混合物：空气、75%一氧化二氮、75%氙气、0.75%异氟烷、0.75%异氟烷加35%或75%一氧化二氮、0.75%异氟烷加30%或60%氙气处理6 h。处死大鼠，用caspase-3免疫染色评估皮质和海马细胞凋亡。在不同的组群中，分离皮质用于半胱天冬酶3、半胱天冬酶8、半胱天冬酶9和细胞色素c的免疫印迹。器官型海马切片出生后的小鼠幼崽衍生和培养24小时前类似的气体暴露，如上所述，随后处理caspase-3 immunostaining.Results：在体内给药的异氟烷增强神经元凋亡。当与异氟烷结合时，一氧化二氮显著增加，而氙气显著降低细胞凋亡至与对照组无差异的值。体外研究证实了氙减弱异氟醚诱导的细胞凋亡的能力。异氟醚增强的内在和常见的凋亡途径的指标的表达，这种增强增加了一氧化二氮，但衰减xeno.Conclusions：目前的研究表明，氙气防止异氟醚诱导的新生儿神经元凋亡。
Background: Anesthetics, including isoflurane and nitrous oxide, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, have been demonstrated to induce apoptotic neurodegeneration when administered during neurodevelopment. Xenon, also an N-methyl-D-aspartate antagonist, not only lacks the characteristic toxicity produced by other N-methyl-D-aspartate antagonists, but also attenuates the neurotoxicity produced by this class of agent. Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis.Methods: Separate cohorts (n = 5 or 6 per group) of 7-day-old rats were randomly assigned and exposed to eight gas mixtures: air, 75% nitrous oxide, 75% xenon, 0.75% isoflurane, 0.75% isoflurane plus 35% or 75% nitrous oxide, 0.75% isoflurane plus 30% or 60% xenon for 6 h. Rats were killed, and cortical and hippocampal apoptosis was assessed using caspase-3 immunostaining. in separate cohorts, cortices were isolated for immunoblotting of caspase 3, caspase 8, caspase 9, and cytochrome c. Organotypic hippocampal slices of postnatal mice pups were derived and cultured for 24 h before similar gas exposures, as above, and subsequently processed for caspase-3 immunostaining.Results: In vivo administration of isoflurane enhances neuronal apoptosis. When combined with isoflurane, nitrous oxide significantly increases whereas xenon significantly reduces apoptosis to a value no different from that of controls. In vitro studies corroborate the ability of xenon to attenuate isoflurane-induced apoptosis. Isoflurane enhanced expression of indicators of the intrinsic and common apoptotic pathways; this enhancement was increased by nitrous oxide but attenuated by xenon.Conclusions: The current study demonstrates that xenon prevents isoflurane-induced neonatal neuronal apoptosis.