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刘长安,汪远金,那莎,朱洁,蔡标.大豆异黄酮对阿尔茨海默病大鼠海马RAGE介导的信号转导通路的影响[J].中国中西医结合杂志,2012,32(6):797-800
大豆异黄酮对阿尔茨海默病大鼠海马RAGE介导的信号转导通路的影响
Effects of Soybean Isoflavones on RAGE Mediated Signal Transduction in the Hippocampus of Rats with Alzheimer’s Disease
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DOI:
中文关键词:  大豆异黄酮  阿尔茨海默氏症  高级糖化终产物受体  磷酸化细胞外信号调节激酶1/2  白细胞介素-6  天冬氨酸特异性半胱氨酸蛋白酶-3
英文关键词:soybean isoflavone  Alzheimer’s disease  receptor of advanced glycosylation end product  phosphorylation extracellular signal-regulated kinase1/2  interleukine 6  cysteine-containing aspartate-specific protease-3
基金项目:安徽省自然科学基金项目年度项目(No.09020103005)
作者单位
刘长安 安徽中医学院中西医结合临床学院生物化学与分子生物学教研室 
汪远金 安徽中医学院中西医结合临床学院生物化学与分子生物学教研室 
那莎 安徽中医学院中西医结合临床学院生物化学与分子生物学教研室 
朱洁 安徽中医学院中西医结合临床学院生物化学与分子生物学教研室 
蔡标 安徽中医学院中西医结合临床学院生物化学与分子生物学教研室 
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中文摘要:
      目的观察大豆异黄酮(soybean isoflavones)对阿尔茨海默病(Alzheimer’s disease,AD)大鼠高级糖化终产物受体(receptor for advanced glycation end products,RAGE)介导的信号转导系统的影响。方法采用β淀粉样蛋白25-35片段(amyloidβ25-35,Aβ25-35)双侧海马注射建立AD大鼠模型,60只大鼠随机分为模型组、大豆异黄酮高剂量组[30mg/(kg·d)]、大豆异黄酮低剂量组[10mg/(kg·d)]、雌激素组[0.4mg/(kg·d)]及假手术组,每组12只。大豆异黄酮高、低剂量组和雌激素组造模后3天灌胃给药(2mL/只),模型组与假手术组给予等体积的0.5%羧甲基纤维素钠(CMC-Na)灌胃,连续21天。酶联免疫吸附法观察各组大鼠海马组织RAGE、白细胞介素-6(interleukin-6,IL-6)的含量。分光光度法检测大鼠海马组织天冬氨酸特异性半胱氨酸蛋白酶-3(cysteine-containing aspartate-specific protease-3,Caspase-3)活性。免疫组织化学法观察大鼠海马组织磷酸化细胞外信号调节激酶1/2(phosphorylation extracellular signal-regulatedkinase1/2,P-ERK1/2)的表达。结果与模型组比较,大豆异黄酮可显著降低AD大鼠海马RAGE蛋白、IL-6含量、Caspase-3活性及ERK1/2蛋白磷酸化水平(P<0.01)。结论大豆异黄酮对AD大鼠海马组织RAGE介导的炎症信号通路具有下调作用,减弱炎症反应,降低Aβ的神经毒性,抵抗海马神经元凋亡。
英文摘要:
      Objective To investigate the effects of soybean isoflavones on receptor for advanced glycation end products(RAGEs) mediated signal transduction in the hippocampus of rats with Alzheimer’s disease(AD).Methods AD rat model was established by bilateral hippocampus injection of amyloid β25-35(Aβ25-35).Sixty rats were equally randomized into 5 groups,i.e.,the model group,the high dose soybean isoflavones group(at the daily dose of 30 mg/kg),the low dose soybean isoflavones group(at the daily dose of 10 mg/kg),the estrogen group(at the daily dose of 0.4 mg/kg),and the sham-operation control group.Three days after modeling 2 mL soybean isoflavones or estrogen was respectively administrated to rats in the high dose soybean isoflavones group,the low dose soybean isoflavones group,and the estrogen group by gastrogavage.Equal volume of 0.5% CMC-Na was administered to rats in the model group and the sham-operation group.The treatment lasted for 21 days.The contents of RAGE and interleukin-6(IL-6) in the hippocampus were measured by ELISA.The activity of cysteine-containing aspartate-specific protease-3(Caspase-3) was measured by spectrophotometry.The expressions of phosphorylation extracellular signal-regulated kinase1/2(P-ERK1/2) in the hippocampus were measured by immunohistochemical assay.Results Compared with the model group,soybean isoflavones could significantly decrease the contents of RAGE and IL-6,the activity of Caspase-3,and the phosphorylation level of ERK1/2 in the hippocampus of AD model rats(P<0.01).Conclusion Soybean isoflavones could down-regulate RAGE mediated inflammatory signal transduction in the hippocampus of AD rats,attenuate the inflammatory reactions,reduce the neurotoxicity of Aβ,and resist the apoptosis of hippocampal neurons.
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