南宝,周缜,汪贯习,等.褐藻胶对Wilson病小鼠的神经保护作用机制研究[J].中国海洋药物,2022,41(4):36-44.
褐藻胶对Wilson病小鼠的神经保护作用机制研究
The neuroprotective effect and mechanism of Algin for Wilson’s disease in mice
投稿时间:2021-07-27  修订日期:2021-10-08
DOI:
中文关键词:  褐藻胶  Wilson病  铜离子  NF-κB  MMP-9
English Keywords:Algin  Wilson’s Disease (WD)  Copper ion (Cu2+)  NF-κB, MMP-9
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作者单位E-mail
南宝 青岛大学医学部中西医结合中心 304678616@qq.com 
周缜 青岛大学医学部中西医结合中心 304678616@qq.com 
汪贯习 青岛大学医学部中西医结合中心 304678616@qq.com 
葛科立 青岛大学医学部中西医结合中心 304678616@qq.com 
王发合 青岛明月海藻集团有限公司 304678616@qq.com 
邱霞 青岛明月海藻集团有限公司 304678616@qq.com 
郭云良* 青岛大学医学部中西医结合中心 guoqdsd@163.com 
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中文摘要:
      目的:探讨褐藻胶对Wilson’s病(WD)小鼠基底节豆状核变性的神经保护作用和机制。方法:健康雄性昆明小鼠,应用铜负荷饮食法建立HLD模型。治疗组每天给予褐藻胶灌胃,对照组动物同步给予等体积的生理盐水灌胃,每日1次,连续28天周。电感耦合等离子体质谱法检测尿铜水平,血液分析仪计数血常规指标,生化分析仪检测肝肾功指标(ALT、AST、Urea、Crea),甲苯胺蓝染色法观察豆状核神经细胞的病理变化,TUNEL法检测细胞凋亡,免疫组化法检测核转录因子-κB(NF-κB)和基质金属蛋白酶-9(MMP-9)的表达。结果:经褐藻胶干预后,高剂量组小鼠行为功能较模型组显著改善,尿铜水平较模型组显著降低(P<0.05),血清ALT、AST活性较模型组均显著下降(P<0.05),变性细胞指数和凋亡细胞指数较模型组均显著降低(P<0.05),NF-κB和MMP-9表达水平较模型组均显著减弱(P<0.05)。结论:褐藻胶可能通过促进铜离子的排泄,抑制铜离子引起的氧化应激和炎症反应,对基底节豆状核神经细胞发挥保护作用。
English Summary:
      To explore the neuroprotective effect and mechanism of Algin on the degeneration in basal ganglia lenticular nucleus of Wilson’s disease (WD) mice. Methods: Adult healthy male Kunming mice were established with HLD models by copper sulfate-loaded diet method. The Algin was given by gavage each day for 28 days; while the mice of control groups were orally given same amount of normal solution at the same time for 28 days. The concentration of copper ion in urine was determined by inductively coupled plasma-mass spectrometry. The blood routine indexes were counted by automatic blood analyzer, and the hepatic and renal functional indexes (ALT, AST, Urea, Crea) were detected by automatic biochemical analyzer. The pathological changes of nerve cells in basal ganglia lenticular nucleus were observed by toluidine blue staining and the neuronal apoptosis detected by TUNEL assay. The immunohistochemical assay was used to determined the expression levels of nuclear factor κB (NF-κB) and matrix mentalloproteinase-9 (MMP-9). Results: After treatment with Algin, the behavioral functions of mice in high-dose group improved significantly than those in the model group; the concentration of copper ion in urine and the hepatic functional indexes (ALT and AST) were significantly decreased than those in the model group (P<0.05). The degenerated cell index and apoptotic cell index decreased, while the expression levels of NF-κB and MMP-9 in basal ganglia lenticular nucleus weakened significantly than those in the model group (P<0.05). Conclusion: Algin could play a neuroprotective effect for nerve cells in basal ganglia lenticular nucleus by promoting Cu2+ excretion and inhabiting oxidant stress and inflammatory reaction induced by Cu2+.
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