益母草碱改善三氯化铝所诱导阿尔茨海默病小鼠学习记忆能力的作用机制  

Leonurine improves learning and memory abilities in mice with Alzheimer’s disease induced by aluminum trichloride through anti-inflammatory and antioxidant properties

作　　者：雷洁昕 陈鹏[2] 周本宏[2] LEI Jiexin;CHEN Peng;ZHOU Benhong(Department of Endocrinology,Renmin Hospital of Wuhan University,Hubei,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院内分泌科,武汉市430060 [2]武汉大学人民医院药学部

出　　处：《河北医药》2024年第15期2251-2255,共5页Hebei Medical Journal

基　　金：国家自然科学基金(编号:31770381);武当山武当特色中药研究湖北省重点实验室开放基金(编号:WDCM2022006)。

摘　　要：目的 探讨益母草碱对灌胃三氯化铝(AlCl_(3))诱导的阿尔茨海默病(Alzheimer’s disease,AD)小鼠的学习认知水平的影响作用并研究其机制。方法 60只C57小鼠随机分为6组即空白对照组、AlCl3模型组、吡拉西坦阳性对照组、益母草碱高、中、低剂量给药组。小鼠灌胃AlCl3建立AD模型,阳性对照组与益母草碱治疗组每天接受药物灌胃进行干预。50 d后,利用水迷宫实验检测小鼠学习记忆能力,之后检测小鼠脑组织MDA、SOD、T-AOC及GSH-Px含量变化;测定脑组织中TNF-α、IL-6及IL-1β表达水平;脑组织切片进行HE染色,观察益母草碱性对阿尔茨海默病小鼠病理损伤的影响。结果 益母草碱明显减少了小鼠逃避潜伏期(P<0.05)和穿越次数(P<0.05);能显著降低神经元的损伤和抑制神经元的丢失;同时可抑制脑组织MDA生成(P<0.01),提高SOD、GSH-Px及T-AOC等活力表达(P<0.01);有效降低脑组织中TNF-α、IL-6及IL-1β等抗炎因子含量(P<0.01)。此外,益母草碱还能提高小鼠脑内Nrf2与HO-1蛋白表达水平且呈剂量依赖性。结论 益母草碱能有效改善AD小鼠认知功能障碍,其主要作用机制可能与促进Nrf2/HO-1通路活化提高小鼠脑组织抗氧化应激水平等有关。Objective To study the effects of Leonurine on learning and memory abilities of mice with Alzheimer's disease(AD) induced by oral gavage of aluminum chloride(AlCl3) and the underlying mechanism.Methods Sixty C57BL/6 mice were randomly assigned into blank control group,AlCl3 model group,piracetam positive control group,and high-dose,medium-dose and low-dose Leonurine groups.The AD mouse model was made by gavage of AlCl3,and daily oral gavage of piracetam and Leonurine was applied in corresponding groups.After 50 days of modeling,water maze test was used to detect the learning and memory abilities of AD mice.Malondialdehyde(MDA),superoxide dismutase(SOD),total antioxidant capacity(T-AOC) and glutathione peroxidase(GSH-Px) in brain tissues were detected.The expression levels of tumor necrosis factor alpha(TNF-α),interleukin 6(IL-6) and IL-1β in brain tissues were determined.The hematoxylin and eosin(H&E) staining of brain sections was performed to observe the effect of Leonurine on pathological injury of AD mice.Results Leonurine could significantly reduce escape latency(P<0.05) and crossing times(P<0.05).Leonurine could significantly reduce the damage of neurons and inhibit the loss of neurons.Furthermore,Leonurine significantly decreased MDA content in brain tissue(P<0.01),and increased SOD,GSH-Px and T-AOC activities(P<0.01).The expression levels of TNF-α,IL-6 and IL-1β in brain tissue were significantly inhibited by Leonurine treatment(P<0.01).In addition,Leonurine upregulated protein levels of nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1) in brain tissue of AD mice dose-dependently.Conclusion Leonurine can improve the learning and memory abilities of AD mice by enhancing anti-oxidative stress in the brain by activating the Nrf2/HO-1 pathway.

关 键 词：益母草碱 抗氧化 抗炎 老年痴呆 学习记忆 

分 类 号：R74[医药卫生—神经病学与精神病学]