首页|石菖蒲挥发油成分改善阿尔茨海默病症状的作用及机制研究

石菖蒲挥发油成分改善阿尔茨海默病症状的作用及机制研究

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目的 探讨石菖蒲挥发油成分(β-细辛醚、α-细辛醚和丁香酚)改善阿尔茨海默病(AD)症状的作用及机制.方法 30只SD大鼠按随机数字表法分为对照组(等体积橄榄油)、模型组(等体积橄榄油)、β-细辛醚组(50 mg/kg溶于橄榄油)、α-细辛醚组(50 mg/kg溶于橄榄油)和丁香酚组(50 mg/kg溶于橄榄油),每组6只;除对照组予0.9%氯化钠注射液外,其余4组均注射β-淀粉样蛋白(Aβ)1-42构建AD模型.5组大鼠分别给予上述油剂灌胃1次/d,连续21 d.采用旷场实验、Y迷宫实验和Morris水迷宫实验检测大鼠行为学变化,HE染色观察脑组织病理学变化,免疫组化检测脑组织中Aβ、微管相关蛋白(TAU)表达水平,免疫荧光法检测脑组织中离子钙结合衔接分子1(Iba1)、胶质纤维酸性蛋白(GFAP)表达水平,ELISA法测定脑组织中IL-1 β、IL-6和TNF-α含量,qRT-PCR和Western blot法分别检测脑组织中过氧化物酶体增殖物激活受体γ(PPARγ)、核转录因子红系2相关因子2(Nrf2)mRNA及蛋白表达水平.结果 与对照组比较,模型组AD大鼠空间学习和认知记忆能力减弱,脑组织神经细胞损伤严重;脑组织中Aβ、TAU表达水平,IL-1β、IL-6、TNF-α含量,以及Iba1、GFAP表达水平均明显升高,而PPARγ、Nrf2 mRNA及蛋白表达水平均明显降低,差异均有统计学意义(均P<0.05).与模型组比较,β-细辛醚组、α-细辛醚组和丁香酚组AD大鼠空间学习和认知记忆能力增强,脑组织神经细胞损伤减轻;脑组织中Aβ、TAU表达水平,IL-1β、IL-6、TNF-α含量,以及Iba1、GFAP表达水平均明显降低,而PPARγ、Nrf2 mRNA及蛋白表达水平均明显升高,差异均有统计学意义(均P<0.05).结论 石菖蒲挥发油成分可有效改善AD大鼠症状,可能是通过激活PPARγ和Nrf2表达进而抑制炎症反应实现的.
Study on effect and related mechanism of volatile oil constituents of Acori Tatarinowii Rhizoma in ameliorating symptoms of Al-zheimer's disease
Objective To investigate effects and related mechanism of volatile oil constituents of Acori Tatarinowii Rhizoma(β-asarone,α-asarone and eugenol)in ameliorating symptoms of Alzheimer's disease(AD).Methods Thirty SD rats were randomly divided into 5 groups with 6 rats in each group.AD model was induced by intracranial injection of amyloidβ-protein(Aβ)1-42(1 μg/μL),and 0.9%sodium chloride was given to control group.After modeling,the rats of β-asarone group,α-asarone group and eugenol group were administrated by gavage with 50 mg/kg β-asarone,α-asarone or eugenol once a day for 21 d continuously,respectively;while equal volume of olive oil was given to control group and model group.Behavioral tests were conducted by open field test,Y maze test,and Morris water maze test.HE staining was used to observe pathological changes of rat brain tissues.Aβ and microtubule-associated protein(TAU)were detected by immunohistochemistry.Im-munofluorescence was performed to observe ionized calcium blinding adaptor molecule 1(Iba1)and glial fibrillary acidic protein(GFAP)expression in cortical and hippocampal regions of rat brain.ELISA was applied to examine IL-1 β,IL-6,and TNF-α levels.The peroxisome proliferator-activated receptor y(PPARγ)and nuclear factor erythroid 2-related factor 2(Nrf2)mRNA and protein expression were determined by qRT-PCR and Western blot,respectively.Results Compared with control group,the AD rats of model group exhibited reduced spatial learning and cognitive memory abilities,severely damaged neuronal cells.There were higher Aβ,TAU,IL-1 β,IL-6,TNF-α,Iba1,and GFAP expression in brain tissues,and lower PPARγ and Nrf2 mRNA and protein expression levels in AD rats of model group compared to control group(all P<0.05).Compared with model group,β-asarone,α-asarone and eugenol significantly improved spatial learning and cognitive memory abilities of AD rats,attenuated neuronal damage of brain tissues,decreased Aβ and TAU,IL-1 β,IL-6 and TNF-αlevels in brain tissues,as well as Iba1 and GFAP expression in cortical and hippocampal areas,and elevated PPARγ and Nrf2 mRNA and protein expression levels in rat brain tissues(all P<0.05).Conclusion Volatile oil constituents of Acori Tatarinowii Rhizoma are effective in improving symptoms of AD rats,which might be associated with activating PPARγ and Nrf2 expression and inhibiting inflammatory response.

Acori Tatarinowii RhizomaVolatile oilAlzheimer's diseaseInflammatory responsePeroxisome proliferator-activated receptor γ

刘立权、江萌、张伊黎、杨晓佳

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310007 浙江中医药大学附属杭州市中医院药剂科

石菖蒲 挥发油 阿尔茨海默病 炎症反应 过氧化物酶体增殖物激活受体γ

浙江省中医药科技计划项目

2023ZF139

2024

浙江医学
浙江省医学会

浙江医学

CSTPCD
影响因子:0.428
ISSN:1006-2785
年,卷(期):2024.46(11)