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Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease

针刺对阿尔茨海默病模型SAMP8小鼠海马线粒体蛋白质组表达的影响

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Abstract

Objective

To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice models with Alzheimer disease (AD), and to explore the possible protective mechanism of acupuncture on mitochondria.

Methods

Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group, an acupuncture at non-acupoint group and a model group, 20 mice in each group. The 20 male senescence-accelerated mouse/resistance 1 (SAMR1) mice of the same age were used as a normal control group. Shenshu (BL 23), Baihui (GV 20), Xuehai (SP 10) and Geshu (BL 17) were selected for acupuncture intervention in acupuncture at acupoint group. After an 8-week intervention, mitochondrial tissues were extracted from the hippocampus. Differentially expressed proteins were identified by subcellular organelle proteomics. Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.

Results

Compared with the model group, there were 13 differentially expressed protein spots in the acupuncture at acupoint group, of which, 9 were up-regulated, including neurofilament light polypeptide (NFL), actin (cytoplasmic 1, database ID: ACTB), tubulin beta-2A chain (TBB2A), tropomodulin-2 (TMOD2), pyruvate dehydrogenase E1 component subunit beta (PDHE1-β), NADH-ubiquinone oxidoreductase 75 kDa subunit (database ID: NDUS1), heat shock cognate 71 kDa protein (HSC71), pyruvate dehydrogenase E1 component subunit alpha (PDHE1-α) and ATP synthase beta subunit (ATP-β); 4 were down-regulated, including glial fibrillary acidic protein (GFAP), pyruvate dehydrogenase phosphatase 1 (PDP1), mitochondrial-processing peptidase subunit alpha (MMP-α) and adenosine kinase (ADK). According to the information provided in the protein database, most of the differentially expressed proteins involve the regulation of mitochondrial function and structure. The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group (P<0.05). ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group (P<0.05); there was no significant difference between the acupuncture at non-acupoint group and the model group (P>0.05).

Conclusion

Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.

摘要

目的

观察针刺对阿尔茨海默病(AD)模型快速老化小鼠亚系8(SAMP8)小鼠海马线粒体蛋白质组表达的影响, 探寻针刺对线粒体发挥保护作用的可能机制。

方法

将60只6月龄雄性SAMP8小鼠随机分为穴位针刺组、 非穴位针刺组及模型组, 每组20只; 另20只同月龄雄性抗快速老化小鼠亚系1(SAMR1)小鼠作为正常组。 针刺组选取肾俞、 百会、 血海、 膈俞进行针刺干预。 干预8星期后, 提取海马线粒体组织, 采用亚细胞器蛋白质组学技术鉴定差异蛋白质点, Western blot验证部分相关差异蛋白质在海马线粒体中的表达。

结果

与模型组相比, 穴位针刺 组最终得到鉴定的有13个差异蛋白质点, 其中9个上调, 包括神经丝轻链多肽(NFL), 肌动蛋白胞质型1(数据库ID: ACTB), 微管蛋白乙2A链(TBB2A), 原肌球调节蛋白2(TMOD2), 丙酮酸脱氢酶E1β亚单位(PDHE1-β), NADH-泛醌氧化 还原酶75 kDa亚基(数据库ID: NDUS1), 热休克同源物71 kDa蛋白(HSC71), 丙酮酸脱氢酶E1α亚单位(PDHE1-α)和ATP合成酶β亚基(ATP-β); 4个下调, 包括胶质细胞原纤维酸性蛋白(GFAP), 丙酮酸脱氢酶磷酸酶1(PDP1), 线粒体加工肽酶α亚基(MMP-α)和腺苷激酶(ADK)。 根据蛋白质数据库中提供的相关信息, 绝大部分差异蛋白质点主要涉及线粒体功能以及结构的调节。 正常组及穴位针刺组的NFL、 TBB2A表达水平明显高于非穴位针刺组(P<0.05); 穴位针刺组的ATP-β、 NDUS1表达水平明显高于非穴位针刺组(P<0.05); 非穴位针刺组与模型组无明显差别(P>0.05)。

结论

针刺可能是通过调节海马神经元线粒体的结构和功能蛋白来实现对AD的潜在治疗作用。

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Acknowledgments

This work was supported by National Natural Science Foundation of China (国家自然科学基金项目, No. 81202730); the Fundamental Research Funds for the Central Universities (中央高校基本科研业务经费, No. 2012QNZT162); the Natural Science Foundation of Hunan Province (湖南省自然科学基金, No. 2011JJ3097); Science and Technology Project of Traditional Chinese Medicine of Hunan Province (湖南省中医药科技项目, No. 201413).

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Authors and Affiliations

  1. The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Mei-ting Liang  (梁梅亭), Guang-cheng Li  (李广诚), Hong Zhu  (朱宏), Qiong Gong  (龚琼), Ke-li Dong  (董克礼), Cong Long  (龙聪), Ya-yue Li  (李雅悦) & Jiengisnur Sayrash  (萨依腊西·杰恩斯努尔)

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  1. Mei-ting Liang  (梁梅亭)
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Correspondence to Hong Zhu  (朱宏).

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Liang, Mt., Li, Gc., Zhu, H. et al. Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease. J. Acupunct. Tuina. Sci. 16, 67–79 (2018). https://doi.org/10.1007/s11726-018-1026-2

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  • DOI: https://doi.org/10.1007/s11726-018-1026-2

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