【罂粟摘要】右美托咪啶通过α2肾上腺素受体减轻七氟醚所致的神经认知功能障碍
右美托咪啶通过α2肾上腺素受体减轻七氟醚所致的神经认知功能障碍
翻译:任文鑫 编辑:佟睿 审校:曹莹
贵州医科大学 高鸿教授课题组

据报道,七氟醚对发育中的大脑有神经毒性作用。右美托咪啶是一种α2肾上腺素能受体激动剂,临床上用于预防七氟醚引起的儿童焦虑。本研究的目的是确定右美托咪啶是否能预防七氟醚诱导的神经细胞凋亡、神经炎症、氧化应激和神经认知功能障碍。此外,还评估了α2肾上腺素受体在右美托咪啶的神经保护作用中的作用。出生后第6天(P)C57BL/6雄性小鼠随机分为4组,每组6只。用右美托咪定单独或与α2肾上腺素受体抑制剂育亨宾联合预处理小鼠,然后暴露于3%七氟醚和25%氧气中。对照组小鼠要么单独接受生理盐水,要么接受七氟醚暴露。七氟醚暴露后,用免疫组织化学方法检测海马组织切片中裂解的caspase-3的表达。测定海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)β、IL-6和丙二醛水平及超氧化物歧化酶(SOD)活性。在P35,用Morris水迷宫测试每只小鼠的学习和记忆能力。七氟醚暴露后,右美托咪啶可显著降低激活的caspase-3的表达。此外,右美托咪啶还能显著降低海马区肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的水平。在右美托咪啶治疗的小鼠中,SOD活性也以剂量依赖的方式增加。在右美托咪定治疗的小鼠中,丙二醛(MDA)以剂量依赖的方式减少。最后,右旋美托咪啶可逆转七氟醚所致的学习记忆障碍。相比之下,联合应用育亨宾显著减弱了右美托咪啶的神经保护作用。这些结果提示,右美托咪啶对七氟醚诱导的细胞凋亡、炎症、氧化应激和神经认知损害具有神经保护作用,这种保护作用至少部分是通过α2肾上腺素受体介导的。

Dexmedetomidine attenuates sevoflurane-induced
neurocognitive impairment through α2-adrenoceptors
It has been reported that sevoflurane induces neurotoxicity in the developing brain. Dexmedetomidine is an α2 adrenoceptor agonist used for the prevention of sevoflurane-induced agitation in children in clinical practice. The aim of the present study was to determine whether neuroinflammation, oxidative stress and neurocognitive impairment. Additionally, the involvement of α2 adrenoceptors in the neuroprotective effect of dexmedetomidine was assessed. Postnatal day (P)6 C57BL/6 male mice were randomly divided into four groups (n=6 in each group). Mice were pretreated with dexmedetomidine, either alone or together with yohimbine, an α2 adrenoceptor inhibitor, then exposed to 3% sevoflurane in 25% oxygen. Control mice either received normal saline alone or with sevoflurane exposure. Following sevoflurane exposure, the expression of cleaved caspase3 was detected by immunohistochemistry in hippocampal tissue sections. In addition, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and malondialdehyde, as well as superoxide dismutase (SOD) activity in the hippocampus were measured. At P35, the learning and memory abilities were assessed in each mouse using a Morris water maze test. Dexmedetomidine significantly decreased the expression of activated caspase-3 following sevoflurane expo- sure. Moreover, dexmedetomidine significantly decreased the levels of TNF-α, IL-1β and IL-6 in the hippocampus. SOD activity also increased in a dose-dependent manner in dexmedetomidine treated mice. MDA decreased in a dose-dependent manner in dexmedetomidine treated mice. Lastly, sevoflurane induced learning and memory impairment was reversed by dexmedetomidine treatment. By contrast, co-administration of yohimbine significantly attenuated the neuroprotective effects of dexmedetomidine. These findings suggested that dexmedetomidine exerted a neuroprotective effect against sevoflurane induced apoptosis, inflammation, oxidative stress and neurocognitive impairment, which was mediated, at least in part, by α2 adrenoceptors.
