| 黄婷婷,郝冬琳,吴波娜,等.尿酸激活Nrf2-ARE信号通路对帕金森病小鼠的保护作用[J].安徽医药,2019,23(7):1315-1319. |
| 尿酸激活Nrf2-ARE信号通路对帕金森病小鼠的保护作用 |
| Neuroprotective effect of uric acid on Parkinson disease mice through Nrf2-ARE signaling pathway |
| 投稿时间：2017-10-13 |
| DOI： |
| 中文关键词: 帕金森病 尿酸 氧化应激 神经炎症 核因子E2相关因子2 黑质 多巴胺能神经元 |
| 英文关键词: Parkinson's disease (PD) uric acid oxidative stress neuroinflammation nuclear factor E2 related factor 2 (Nrf2) substantia nigra dopaminergic neurons |
| 基金项目:常州市武进区科技支撑计划（WS201504） |
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| 中文摘要: |
| 目的 探讨尿酸对帕金森病(PD)小鼠的神经保护作用以及对核因子E2相关因子2(Nrf2)的调控作用。方法 雄性C57BL/6J小鼠(6~8周、20~25 g)30只,采用随机数字表法分为三组:对照组(生理盐水)、1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)组、尿酸组(尿酸+MPTP),每组各10只。MPTP组小鼠经腹腔注射MPTP(20 mg/kg),每天1次,连续7 d。尿酸组于MPTP给药之前2 h腹腔注射尿酸(250 mg/kg),共13 d(MPTP注射前3 d,MPTP注射同时的7 d,MPTP结束后3 d)。对照组接受0.9%生理盐水代替MPTP和尿酸。在第14天测量各组小鼠的行为和认知功能,处死小鼠获取脑组织,免疫荧光染色测定黑质酪氨酸羟化酶(TH)的表达。实时荧光定量PCR检测Nrf2及下游基因mRNA的表达。免疫组化检测海马白细胞介素-1β(IL-1β)表达。酶联免疫吸附试验(ELISA)检测血清和海马IL-1β、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平。结果 尿酸能改善PD小鼠的行为学和认知功能,增加黑质TH阳性多巴胺能神经元数目和纹状体多巴胺含量。尿酸增加Nrf2和Nrf2下游基因mRNA的表达,包括γ-GCLC、HO-1和NQO1。尿酸显著提高MPTP处理小鼠黑质区SOD、CAT、GSH含量,降低MDA含量。尿酸抑制海马组织IL-1β蛋白的表达,并降低血清和海马中IL-1β、IL-6和TNF-α水平。结论 尿酸对PD小鼠多巴胺能神经元显示神经保护特性,其机制可能与尿酸通过激活Nrf2-ARE通路及调节神经炎症和氧化应激有关。 |
| 英文摘要: |
| Objective The purpose of this study was to investigate the in vivo neuroprotective effect of uric acid,and its modulation on Nrf2.Methods PD was induced in male C57BL/6 mice through intraperitoneal injection with MPTP (20 mg/kg) for 7 d,and divided into control,MPTP (saline) and uric acid groups (250 mg/kg).Behavioral and cognitive functions were measured at d 14.Mice were killed and brain tissues were obtained.Immunofluorescent staining was used to detect tyrosine hydroxylase (TH) expression.Real-time quantitative PCR was used to measure the mRNA expressions of Nrf2 and its downstream genes.Immunohistochemistry was used to detect the expression of interleukin-1β (IL-1β) in hippocampus.Enzyme-linked immunosorbent assay (ELISA) was used to detect serum and hippocampal levels of IL-1β,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α).Results Uric acid can improve the behavioural and cognitive functions of PD mice,increase the TH positive neurons in substantia nigra and dopamine content in striatum.The mRNA expressions of Nrf2,γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC),heme oxygenase-1 (HO-1) and NQO1 can be elevated by uric acid.Uric acid can increase superoxide dismutase (SOD),catalase (CAT),glutathione (GSH) levels and decrease malondialdehyde (MDA) content in substantia nigra of MPTP mice.Uric acid can inhibite the expression of IL-1β in hippocampus and decrease the levels of IL-1β,IL-6 and TNF-α in serum and hippocampus of MPTP mice.Conclusion Uric acid shows neuroprotective properties in dopaminergic neurons of PD mice by activating Nrf2-ARE pathway and modulating neuroinflammation and oxidative stress. |
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