纳米氧化铈对48小时睡眠剥夺雄性小鼠认知功能的影响

Effects of cerium oxide nanoparticles on cognitive function in 48 h sleep deprived male mice

目的研究纳米氧化铈(cerium oxide nanoparticles,CeO_2NPs)对48 h睡眠剥夺小鼠认知功能的影响,并探讨其作用机制。方法将36只4周龄雄性健康清洁级ICR小鼠分为6组:空白对照组,溶剂对照组,睡眠剥夺对照组,CeO_2NPs低、中、高剂量组。空白对照组灌胃1 mL蒸馏水,溶剂对照组和睡眠剥夺对照组灌胃1 mL 1%羧甲基纤维素钠溶液,CeO_2NPs低、中、高剂量组分别灌胃1 mL 4、8和16 mg/kg的纳米氧化铈溶液,连续30天。第31天,采用单平台水环境法进行48 h睡眠剥夺。继之,利用Y-型迷宫试验确定各组小鼠的认知能力,同时测定小鼠大脑过氧化氢酶(CAT)活性、丙二醛(MDA)含量、总抗氧化能力(T-AOC)水平及一氧化氮(NO)和谷氨酸(Glu)含量。结果与溶剂对照组比较,48 h睡眠剥夺小鼠的认知能力[(36±2)次vs.(20±2)次,P=0.0006;10.753%±0.031%vs.24.927%±0.972%,P=0.00000045]、大脑CAT酶活性[(78.151±17.683)nmol/mg prot vs.(198.155±14.437)nmol/mg prot,P=0.0008]、T-AOC水平[(103.630±24.209)U/mg prot vs.(264.599±50.223)U/mg prot,P=0.007]降低,大脑MDA含量[(9.499±1.249)nmol/mg prot vs.(6.157±0.373)nmol/mg prot,P=0.0113]、NO水平[(11.608±1.281)μmol/mg prot vs.(3.628±1.064)μmol/mg prot,P=0.001]和Glu含量[(4.731±0.131)μg/mg prot vs.(4.476±0.126)μg/mg prot,P=0.03]增加。与睡眠剥夺对照组比较,CeO_2NPs低、中、高剂量组48 h睡眠剥夺小鼠的认知能力均有所改善,其中中剂量组小鼠的认知能力改善最显著[(27±2)次vs.(36±2)次,P=0.005;18.743%±0.245%vs.10.753%±0.031%,P=0.0000006],同时在提高大脑CAT活性[(238.065±19.393)nmol/mg prot vs.(78.151±17.683)nmol/mg prot,P=0.00045]、T-AOC水平[(210.516±11.339)U/mg prot vs.(103.630±24.209)U/mg prot,P=0.002],降低大脑MDA[(6.528±1.162)nmol/mg prot vs.(9.499±1.249)nmol/mg prot,P=0.039]、NO[(5.651±0.239)μmol/mg prot vs.(11.608±1.281)μmol/mg prot,P=0.001]和Glu[(4.358±0.016)μg/mg prot vs.(4.731±0.131)μg/mg prot,P=0.008]含量方面的影响也最显著。结论纳米氧化铈可以改善睡眠剥夺雄性小鼠的认知能力,这可能与其提高了大脑抗氧化能力,降低了自由基对脑部神经的损伤,调节了大脑的神经递质有关。

Objective To study the effects of cerium oxide nanoparticles（ CeO2 NPs）on cognitive function in 48 hours of sleep deprived male mice and explore its mechanism.Methods Thirty-six healthy clean ICR male mice（ four weeks old） were randomly divided into 6 groups： blank control group,solvent control group,sleep deprivation control group,low,medium and high dose groups of CeO2 NPs. 1 m L of distilled water were given to mice of blank group,1 m L of solvent were given to mice of solvent control and sleep deprivation control group,1 mL of CeO2 NPs solvent（ 4,8,16 mg/kg） were administered to mice of low,medium and high dose groups of CeO2 NPs. Each group of mice received intragastric administration for 30 days. On the 31 st day,a single platform water environment method was used for 48 hours of sleep deprivation on mice. Then,the cognitive ability of the mice was tested by Y-maze. Further,the antioxidant（ CAT,MDA,T-AOC） and neurotransmitters（ NO,Glu） in mice brain tissue were measured also.Results Compare with the solvent control group,48 hours of sleep deprivation reduced the cognitive ability of mice [（ 36 ± 2） times vs.（ 20 ± 2） times,P = 0. 0006; 10. 753%± 0. 031% vs. 24. 927% ± 0. 972%,P = 0. 00000045 ],CAT activity [（ 78. 151 ±17. 683） nmol/mg prot vs.（ 198. 155 ± 14. 437） nmol/mg prot,P = 0. 0008]and the level of T-AOC [（ 103. 630 ± 24. 209） U/mg prot vs.（ 264. 599 ± 50. 223） U/mg prot,P =0. 007],but improved the content of MDA [（ 9. 499 ± 1. 249） nmol/mg prot vs.（ 6. 157± 0. 373） nmol/mg prot,P = 0. 0113 ],NO [（ 11. 608 ± 1. 281） μmol/mg prot vs.（ 3. 628 ± 1. 064） μmol/mg prot,P = 0. 001]and Glu[（ 4. 731 ± 0. 131） μg/mg prot vs.（ 4. 476 ± 0. 126） μg/mg prot,P = 0. 03] in the brain. Low,medium and high dose Ce O2 NPs enhanced cognitive performance of the sleep deprived mice. Among three dose groups,the medium dose groups most significantly improved the cognitive ability of mice[（ 27 ± 2） times vs.（ 36 ± 2） times,P = 0. 005; 18. 743% ± 0. 245% vs. 10. 753% ±0. 031%,P = 0. 0000006 ],increased CAT activities [（ 238. 065 ± 19. 393） nmol/mg prot vs.（ 78. 151 ± 17. 683） nmol/mg prot,P = 0. 00045] and T-AOC levels [（ 210. 516± 11. 339） U/mg prot vs.（ 103. 630 ± 24. 209） U/mg prot,P = 0. 002],decreased MDA[（ 6. 528 ± 1. 162） nmol/mg prot vs.（ 9. 499 ± 1. 249） nmol/mg prot,P = 0. 039],NO[（ 5. 651 ± 0. 239） μmol/mg prot vs.（ 11. 608 ± 1. 281） μmol/mg prot,P = 0. 001]and Glu levels [（ 4. 358 ± 0. 016） μg/mg prot vs.（ 4. 731 ± 0. 131） μg/mg prot,P = 0. 008].Conclusion Ce O2 NPs can improve the cognitive ability of sleep deprived male mice,improve the antioxidant capacity of brain,reduce free radical damage to the nerves of brain,and regulate the neurotransmitters of brain.