摘要
目的探讨褐藻胶对Wilson病(WD)小鼠基底节豆状核变性的神经保护作用和机制。方法应用铜负荷饮食法建立WD模型,治疗组小鼠每天给予褐藻胶灌胃,对照组同步灌胃等体积的生理盐水,每日1次,连续28 d。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,原位缺口末端标记法(TUNEL)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。
Objective To explore the neuroprotective effect and mechanism of algin on the degenerative nerve cells in basal ganglia lenticular nucleus(BGLN)of Wilson’s disease(WD)mice.Methods Adult healthy male Kunming mice were established with WD models by copper sulfate-loaded diet method.The algin was given by gavage 1 time a 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 BGLN were observed by toluidine blue staining and the nerve apoptosis detected by Terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)assay.The immunohistochemical assay was used to determined the expression levels of nuclear factorκB(NF-κB)and matrix mentalloproteinase-9(MMP-9).Results After interfering with algin,the behavioral functions of mice in high-dose group improved more significantly than those in the model group;the level of copper ion in urine and the activities of ALT and AST in serum were more 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 BGLN weakened more significantly than those in the model group(P<0.05).Conclusion Algin could play a neuroprotective effect for nerve cells in BGLN by promoting Cu^(2+)excretion and inhabiting oxidant stress and inflammatory reaction induced by Cu^(2+).
作者
南宝
周缜
汪贯习
葛科立
王发合
邱霞
郭云良
NAN Bao;ZHOU Zhen;WANG Guan-xi;GE Ke-li;WANG Fa-he;QIU Xia;GUO Yun-liang(Institute of Integrative Medicine,Qingdao University Medical College,Qingdao 266021,China;Department of Medical Records,The First Municipal Hospital of Zibo,Zibo 255299,China;State Key Laboratory of Bioactive Seaweed Substances,Qingdao Brightmoon Seaweed Group Co.Ltd.,Qingdao 266400,China)
出处
《中国海洋药物》
CAS
CSCD
2022年第4期36-44,共9页
Chinese Journal of Marine Drugs
基金
青岛西海岸新区科技项目(2020-3-2)
青岛市中医药科研项目(2019-ZYY-065,2020-ZYY-047)资助。
