铁观音对阿尔茨海默病小鼠行为的影响及机制

doi:10.3785/j.issn.1008-9209.2021.05.191

浙江大学学报（农业与生命科学版）

2022, Vol. 48

Issue (1): 68-77 DOI: 10.3785/j.issn.1008-9209.2021.05.191

动物科学与动物医学

铁观音对阿尔茨海默病小鼠行为的影响及机制

姜炫旭¹(

),周辉¹,叶钰珊¹,刘仲华²,魏月德³,杨江帆⁴,金恩惠¹,何普明¹,李博¹,吴媛媛¹,屠幼英¹(

)

^1.浙江大学农业与生物技术学院茶学系，杭州 310058
^2.湖南农业大学，教育部茶学重点实验室，长沙 410128
^3.福建安溪岐山魏荫名茶有限公司，福建泉州 362431
^4.福建农林大学园艺学院，福州 350002

Effects and mechanisms of Tieguanyin on the behavior of Alzheimer’s disease APP/PS1 mice

Hyunuk KANG¹(

),Hui ZHOU¹,Yushan YE¹,Zhonghua LIU²,Yuede WEI³,Jiangfan YANG⁴,Eunhye KIM¹,Puming HE¹,Bo LI¹,Yuanyuan WU¹,Youying TU¹(

)

^1.Department of Tea Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China
^2.Key Laboratory of Tea Science of Education of Ministry, Hunan Agricultural University, Changsha 410128, China
^3.Fujian Anxi Qishan Weiyin Famous Tea Co. , Ltd. , Quanzhou 362431, Fujian, China
^4.College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China

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摘要：

研究清香型铁观音（Tgy-Q）、浓香型铁观音（Tgy-N）和陈香型铁观音（Tgy-C）对APP/PS1双转基因阿尔茨海默病（Alzheimer’s disease, AD）小鼠行为学的改善作用，及其对AD小鼠氧化应激及炎症等的作用机制。以C57BL/6J小鼠10只作为对照，6月龄雌性APP/PS1小鼠40只分成模型组、多奈哌齐组、Tgy-Q、Tgy-N和Tgy-C组，连续70 d灌胃给药，进行Y迷宫和旷场行为学实验，结束后处死，收集血浆和脑组织，检测小鼠血浆中超氧化物歧化酶活性、谷胱甘肽过氧化物酶活性和丙二醛含量，并通过免疫组化实验观察胶质细胞的形态变化。Y迷宫实验结果表明，3组铁观音提取物处理组小鼠自发交替反应率分别比模型组增加17.3%、17.6%、19.8%（P＜0.001），各组小鼠工作记忆能力较模型组有显著提高。旷场实验结果发现：与模型组相比，Tgy-C组小鼠中央区域的运动距离增加93.0%，Tgy-N组增加82.0%，Tgy-Q组增加49.2%；中央区域停留时间以Tgy-C组小鼠的效果最佳，增加105.0%（P＜0.01），其次为Tgy-N组，增加84.1%（P＜0.01），Tgy-Q组增加66.8%（P＜0.05）。Tgy-C组小鼠的空间探索能力及焦虑行为改善更好。本实验中氧化应激水平下降是抗AD作用的主要作用机制。研究发现，与模型组组比，Tgy-Q、Tgy-N、Tgy-C处理的小鼠血浆丙二醛含量分别降低18.44%、12.97%、15.11%；超氧化物歧化酶活性分别升高15.31%、13.69%、18.80%。免疫组化实验结果表明，3种铁观音提取物对AD小鼠脑部小胶质细胞和星型胶质细胞形态的恢复有改善作用。综上所述，铁观音提取物对AD小鼠模型具有一定的缓解或保护作用，为科学饮用铁观音提取物抗AD功效提供了新的理论依据。

关键词： 不同香型铁观音; 阿尔茨海默病; 认知功能; 氧化应激; 炎症

Abstract:

The effects of Tieguanyin extracts from different fragrance types (Qingxiang, Tgy-Q; Nongxiang, Tgy-N; and Chenxiang, Tgy-C) on the behavior of APP/PS1 double transgenic Alzheimer’s disease (AD) mice were studied, and the mechanisms of oxidative stress and inflammation were analyzed. Forty six-month-old female APP/PS1 mice were equally divided into five groups, which named as model group, donepezil group, Tgy-Q, Tgy-N and Tgy-C groups, and the control group consisted of 10 C57BL/6J mice. The drug was given by oral gavage for 70 consecutive days, and Y-maze test and open field test were performed during administration. At the end of the behavioral study, they were executed, and their plasma and brain tissue were collected, and then the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) content in plasma of mice were determined, and the morphological changes of glial cells were observed by immunohistochemical assay. The spontaneous alternation behavior rates of Tgy-Q, Tgy-N, Tgy-C extract treatments in the Y-maze experiment of mice groups were increased by 17.3%, 17.6% and 19.8% compared with the model group, respectively (P＜0.001), and the learning and memory abilities of mice in each group were significantly improved as compared with the model group. The results of open field test showed that the movement distances and residence time in the central area of mice fed with Tieguanyin extracts were significantly increased. The effective movement distances in the central area of mice was increased by 93.0% in the Tgy-C group (P＜0.001), followed by 82.0% in the Tgy-N group (P＜0.001) and 49.2% in the Tgy-Q group (P＜0.001). The optimal retention time in the central area of mice was 105.0% in the Tgy-C group (P＜0.01), followed by 84.1% in the Tgy-N group (P＜0.01), and 66.8% in the Tgy-Q group (P＜0.05). In the open field test, the spatial exploration ability and anxiety behavior of Tgy-C group were the best in all the treatments. In this experiment, oxidative stress levels of three Tieguanyin treatments were decreased, which are the main mechanisms of Tieguanyin against Alzheimer’s disease of APP/PS1 mice. Compared with the model group, the MDA contents of plasma in the Tgy-Q, Tgy-N, Tgy-C treatments were significantly reduced by 18.44%, 12.97% and 15.11%, respectively, and the SOD activities in the three groups were increased by 15.31%, 13.69% and 18.80%, respectively. Tieguanyin extracts also improved the morphological recovery of microglia and astrocytes in the brain of AD mice. The above research results indicate that three Tieguanyin extracts had a certain alleviating or protective effect on AD mice.

Key words: Tieguanyin with different fragrance types Alzheimer’s disease cognitive function oxidative stress inflammation

收稿日期: 2021-05-19 出版日期: 2022-03-04

CLC:

S 571.1

基金资助: 国家重点研发计划(2017YFD0400800);福建省“2011协同创新中心”项目;浙江大学国际茶学联合研究中心项目（K横20192450）

通讯作者: 屠幼英 E-mail: 11616111@zju.edu.cn;youytu@zju.edu.cn

作者简介: KANG Hyunuk（https://orcid.org/0000-0001-5609-4243），E-mail：11616111@zju.edu.cn

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引用本文:

姜炫旭,周辉,叶钰珊,刘仲华,魏月德,杨江帆,金恩惠,何普明,李博,吴媛媛,屠幼英. 铁观音对阿尔茨海默病小鼠行为的影响及机制[J]. 浙江大学学报（农业与生命科学版）, 2022, 48(1): 68-77.

Hyunuk KANG,Hui ZHOU,Yushan YE,Zhonghua LIU,Yuede WEI,Jiangfan YANG,Eunhye KIM,Puming HE,Bo LI,Yuanyuan WU,Youying TU. Effects and mechanisms of Tieguanyin on the behavior of Alzheimer’s disease APP/PS1 mice. Journal of Zhejiang University (Agriculture and Life Sciences), 2022, 48(1): 68-77.

链接本文:

https://www.zjujournals.com/agr/CN/10.3785/j.issn.1008-9209.2021.05.191 或 https://www.zjujournals.com/agr/CN/Y2022/V48/I1/68

表1 供试小鼠的灌胃给药方案

图1 铁观音提取物对APP/PS1小鼠Y迷宫行为的影响A.正常组；B.模型组；C.多奈哌齐组；D.清香型铁观音组；E.浓香型铁观音组；F：陈香型铁观音组（下同）。与正常组相比，###表示在P＜0.001水平差异有极高度统计学意义；与模型组相比，**和***分别表示在P＜0.01和P＜0.001水平差异有高度统计学和极高度统计学意义。

图2 各组小鼠运动的总距离与正常组相比，###表示在P＜0.001水平差异有极高度统计学意义；与模型组相比，**表示在P＜0.01水平差异有高度统计学意义。

图3 各组小鼠在中央区的运动距离及时间与正常组相比，###表示在P＜0.001水平差异有极高度统计学意义；与模型组相比，*、**和***分别表示在P＜0.05、P＜0.01和P＜0.001水平差异有统计学、高度统计学和极高度统计学意义。

图4 各组小鼠旷场实验运动轨迹图

图5 铁观音提取物对APP/PS1小鼠血浆抗氧化能力的影响与正常组相比，##和###分别表示在P＜0.01和P＜0.001水平差异有高度统计学和极高度统计学意义；与模型组相比，*、**和***分别表示在P＜0.05、P＜0.01和P＜0.001水平差异有统计学、高度统计学和极高度统计学意义。

图6 免疫组化观察铁观音提取物对APP/PS1小鼠脑内GFAP蛋白表达的影响

图7 免疫组化观察铁观音提取物对APP/PS1小鼠脑内Iba-1蛋白表达的影响

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