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氧化镁和氧化锌纳米粒子通过调节应激和非应激大鼠海马中的谷氨酸水平和 NMDA 受体表达发挥镇痛作用。

MgO and ZnO nanoparticles anti-nociceptive effect modulated by glutamate level and NMDA receptor expression in the hippocampus of stressed and non-stressed rats.

机构信息

Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

出版信息

Physiol Behav. 2020 Feb 1;214:112727. doi: 10.1016/j.physbeh.2019.112727. Epub 2019 Oct 30.

DOI:10.1016/j.physbeh.2019.112727
PMID:31676262
Abstract

The anti-nociceptive mechanisms of MgO and ZnO nanoparticles have not been thoroughly investigated; in this study, we evaluated the effects of anti-nociceptive dose of MgO and ZnO NPs on glutamate level and NMDA receptor subunits expression (NR1, NR2 and NR2B) in the rat whole hippocampus with and without acute restraint stress. Adult rats were divided into control, MgO and ZnO NPs 5 mg/kg, the stress of 90 min alone and with MgO or ZnO NPs 5 mg/kg groups. All components injected intraperitoneally and the nociceptive response was measured with hot plate apparatus 90 min after injections or stress induction. Magnesium, zinc, glutamate levels and NMDA receptor subunits expression were measured in the animal hippocampus. MgO NPs, ZnO NPs and acute stress induced anti-nociceptive effect. MgO NPs observably decreased glutamate and increased magnesium levels and NR2B subunit expression. ZnO NPs decreased glutamate level. Stress elevated endogenous magnesium and zinc levels and also the NR2B expression, but did not change glutamate level. MgO and ZnO NPs in the presence of stress increased the glutamate level and ZnO NPs increased the zinc and the NR2A expression. Stress decreased endogenous magnesium in the hippocampus. MgO and ZnO NPs could affect pain perception by changing glutamate level in the whole hippocampus tissue, while ion level changes followed by injection could probably affect the gene expression in the presence and the absence of stress. It seems that stress indirectly could adverse nanoparticles effects on glutamate level and increase zinc ion releasing from ZnO NPs by activating the gene expression without affecting pain perception.

摘要

氧化镁和氧化锌纳米粒子的抗伤害感受机制尚未得到彻底研究;在本研究中,我们评估了抗伤害感受剂量的氧化镁和氧化锌纳米粒子对谷氨酸水平和 NMDA 受体亚基表达(NR1、NR2 和 NR2B)的影响,以及在急性束缚应激前后大鼠全海马中的作用。成年大鼠分为对照组、氧化镁和氧化锌 NPs 5mg/kg 组、单独应激 90min 组和应激同时给予氧化镁或氧化锌 NPs 5mg/kg 组。所有成分均经腹腔注射,注射或应激诱导 90min 后用热板仪测量疼痛反应。测量动物海马中的镁、锌、谷氨酸水平和 NMDA 受体亚基表达。氧化镁 NPs、氧化锌 NPs 和急性应激诱导抗伤害感受作用。氧化镁 NPs 明显降低谷氨酸水平,增加镁水平和 NR2B 亚基表达。氧化锌 NPs 降低谷氨酸水平。应激增加内源性镁和锌水平,并增加 NR2B 表达,但不改变谷氨酸水平。在应激存在的情况下,氧化镁和氧化锌 NPs 增加了谷氨酸水平,而氧化锌 NPs 增加了锌和 NR2A 表达。应激降低了海马中的内源性镁。氧化镁和氧化锌 NPs 可通过改变全海马组织中的谷氨酸水平来影响痛觉感知,而注射后离子水平的变化可能会在存在和不存在应激的情况下影响基因表达。应激似乎通过激活基因表达间接影响 NMDA 受体亚基表达,从而增加来自 ZnO NPs 的锌离子释放,而不影响疼痛感知,从而对谷氨酸水平产生不利影响。

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