芍药苷活化Nrf2/ARE通路减轻Aβ_(1-42)诱导的大鼠海马神经元损伤  

Peoniflorin activates Nrf2/ARE pathway to alleviate the Aβ_(1-42)-induced hippocampal neuron injury in rats

作　　者：钟树志[1] 马世平[2] 洪宗元[3] 

机构地区：[1]皖南医学院组织胚胎学教研室,安徽芜湖241002 [2]中国药科大学中药药理学教研室,江苏南京210038 [3]皖南医学院药理学教研室,安徽芜湖241002

出　　处：《药学学报》2013年第8期1353-1357,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金面上项目(81171255);教育部科学技术研究重点项目(208058);安徽高校省级自然科研基金重点项目(KJ2012A271)

摘　　要：Aβ（1-42）是阿尔茨海默病（Alzheimer’s disease，AD）脑内老年斑的主要成分，其诱导氧化应激反应是邶致脑内神经元损伤和死亡的机制之一。芍药苷是中药芍药的主要有效单体成分，具有抗炎、抗氧化、抑制细胞内钙超载、保护神经元等功能。This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 （Nrf2） and its downstream signal molecules in the hippocampus of Alzheimer＇s disease （AD） rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid（1-42） （Aβ（1-42）） and divided randomly into 3 groups： AD model group, peoniflorin low-dose （15 mg ·kg^-1） group and peoniflorin high-dose （30 mg·kg^-1） group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered （ip） once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 （HO-1） and y-glutamylcysteine synthethase （γ-GCS） mRNA by reverse transcription PCR, determining the contents of glutathione （GSH）, malondialdehyde （MDA） and carbonyl protein （CP） using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein （NAIP） and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and γ-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Aβ（1-42）-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.

关 键 词：芍药苷 β-淀粉样蛋白(1-42) 核因子-红系2相关因子-2 神经元凋亡抑制蛋白 Caspase-3 氧化应激 

分 类 号：R963[医药卫生—微生物与生化药学]