Effects of <italic style="font-style: italic">Xixin Decoction</italic> （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ<sub>1-42</sub>，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice

DUAN Liqi; DIWU Yongchang; HAN Xinyue; ZHAO Enlong; ZHANG Hu; WANG Yali; ZHOU Yuan

doi:10.13288/j.11-2166/r.2023.24.013

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Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ_1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice

更新时间：2023-12-12

- Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ_1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice
- Journal of Traditional Chinese Medicine Vol. 64, Issue 24, Pages: 2561-2569(2023)
- 作者机构：
  
  1.陕西中医药大学第一临床医学院，陕西省咸阳市秦都区世纪大道中段1号，712046
  2.陕西中医药大学
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.24.013
  CLC：
- Received：13 June 2023，
  
  Revised：2023-10-04，
  
  Published：17 December 2023
- 稿件说明：
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段力琦,第五永长,韩欣悦等.洗心汤对快速老化模型小鼠肠道菌群多样性及脑肠组织Aβ_1-42、LPS、SAA、ACH水平的影响[J].中医杂志,2023,64(24):2561-2569. DOI: 10.13288/j.11-2166/r.2023.24.013.

DUAN Liqi,DIWU Yongchang,HAN Xinyue,et al.Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ_1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(24):2561-2569. DOI: 10.13288/j.11-2166/r.2023.24.013.
段力琦,第五永长,韩欣悦等.洗心汤对快速老化模型小鼠肠道菌群多样性及脑肠组织Aβ_1-42、LPS、SAA、ACH水平的影响[J].中医杂志,2023,64(24):2561-2569. DOI: 10.13288/j.11-2166/r.2023.24.013. DOI：

DUAN Liqi,DIWU Yongchang,HAN Xinyue,et al.Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ_1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(24):2561-2569. DOI: 10.13288/j.11-2166/r.2023.24.013. DOI：

摘要

目的

探讨洗心汤防治阿尔茨海默病（AD）的可能作用机制。

方法

将50只快速老化模型小鼠（SAMP8）随机分为模型组，益生菌组，洗心汤高、中、低剂量组，每组10只，另取10只同源对抗快速老化小鼠（SAMR1）设为对照组。喂养10周后，洗心汤高、中、低剂量组以洗心汤5.08、2.54、1.27 g/（kg·d）灌胃，益生菌组以复合益生菌冻干粉0.39 g/（kg·d）灌胃，对照组和模型组以蒸馏水10 ml/（kg·d）灌胃，各组每天灌胃1次。灌胃10周后，采用Morris水迷宫试验检测各组小鼠空间学习记忆能力；HE染色观察小鼠海马CA3区、结肠组织病理学改变；ELISA法检测小鼠海马组织和结肠区β淀粉样蛋白

1-42

（Aβ

1-42

）、脂多糖（LPS）、血清淀粉样蛋白A（SAA）、乙酰胆碱（ACH）水平；16S rRNA测序技术检测小鼠粪便中肠道菌群多样性的变化。

结果

与对照组比较，模型组海马和结肠组织Aβ

1-42

、LPS、SAA含量明显升高，ACH含量明显降低（

＜0.05或

＜0.01）。与模型组比较，益生菌组第2、5天的逃避潜伏期明显缩短，洗心汤高剂量组第2~5天逃避潜伏期明显缩短，目标平台象限滞留时间显著增加，洗心汤中剂量组第5天逃避潜伏期明显缩短（

＜0.05或

＜0.01），洗心汤高、中剂量组海马神经元细胞排列较为紧密，海马组织及结肠组织SAA、Aβ

1-42

、LPS含量明显降低，ACH含量明显升高，Simpson、Shannon指数明显升高（

＜0.05或

＜0.01）；益生菌组和洗心汤低剂量组海马神经元细胞排列较为松散，益生菌组和洗心汤高剂量组的拟杆菌门、拟普雷沃氏菌属明显降低，厚壁菌门、乳酸杆菌占比明显升高（

＜0.05或

＜0.01）。与益生菌组和洗心汤高剂量组比较，洗心汤中剂量组杯状细胞数目减少，洗心汤低剂量组腺体数目减少并伴有萎缩。与洗心汤中、低剂量组比较，洗心汤高剂量组海马区Aβ

1-42

含量明显降低，海马区及结肠组织ACH含量明显升高，结肠组织SAA含量降低（

＜0.05或

＜0.01），且洗心汤低剂量组海马区SAA含量明显高于高、中剂量组（

＜0.01）。

结论

洗心汤可以改善SAMP8的空间学习记忆能力，减轻海马、结肠组织中LPS、SAA、Aβ

1-42

的生成与沉积，增加脑肠区ACH的含量，其防治AD的作用机制可能与调节肠道微生态、影响菌群多样性、改善炎症反应有关。

Abstract

Objective

To observe the possible mechanism of

Xixin Decoction

（洗心汤， XXD） in the prevention and treatment of Alzheimer 's disease（AD）.

Methods

Fifty rapid aging model mice （SAMP8） were randomly divided into model group， probiotic group， high-， moderate- and low-dose group of XXD， with 10 mice in each group. Another 10 homologous anti-rapid aging mice （SAMR1） were set as control group. After 10 weeks of feeding， the control group and the model group were given 10 ml·kg

-1

·d

-1

of distilled water by gavage， while the probiotic group （0.39 g·kg

-1

·d

-1

）， the high-dose group of XXD （5.08 g·kg

-1

·d

-1

）， the moderate-dose group of XXD （2.54 g·kg

-1

·d

-1

）， and the low-dose group of XXD （1.27 g·kg

-1

·d

-1

） were given corresponding drugs or decoctions by gavage， once a day in all groups. After 10 weeks of intragastric administration， Morris water maze was used to detect the spatial learning and memory ability of mice in each group. HE staining was used to observe the pathological changes of hippocampal CA3 region and colon. The levels of β-amyloid 1-42 （Aβ

1-42

）， lipopolysaccharide （LPS）， serum amyloid A （SAA） and acetylcholine （ACH） in hippocampus and colon were detected by ELISA.The diversity of intestinal flora in mouse feces was detected by 16S rRNA sequencing.

Results

Compared to those in the control group， the levels of Aβ

1-42

，LPS， SAA increased， while the level of ACH decreased in the model group （

＜0.05 or

＜0.01）. Compared to those in the model group， the escape latency period of the probiotic group was significantly shortened on the 2nd and 5th days， while the escape latency period was shortened， and the residence time in the target platform quadrant increased in the high-dose XXD group during the 2nd to 5th days； the escape latency period was shortened significantly in the moderate-dose XXD group on the 5th day （

＜0.05 or

＜0.01）. Compared to those in the model group， the hippocampal neuron cells in the high- and moderate-dose XXD groups were arranged more closely， with decreased levels of SAA， Aβ

1-42

and LPS， increased ACH level， Simpson and Shannon index （

＜0.05 or

＜0.01）； the arrangement of hippocampal neuron cells in the probiotic group and the low-dose XXD group was relatively loose； the proportions of Bacteroidetes and Prevotella were significantly reduced in the probiotic group and the high-dose XXD group， while that of Firmicutes and Lactobacillus significantly increased （

＜0.05 or

＜0.01）. Compared to those in the probiotic group and the high-dose XXD group， the number of goblet cells in the moderate-dose XXD group decreased， and the number of glands in the low-dose XXD group decreased with atrophy. The high-dose XXD group had decreased Aβ

1-42

level in the hippocampus， increased ACH level in thehippocampus and colon tissue， and decreased SAA in the colon tissue than the moderate- and low-dose XXD groups （

＜0.05 or

＜0.01）； moreover， the SAA level in the hippocampus was significantly higher in the low-dose XXD group than the high- and moderate-dose groups （

＜0.01）.

Conclusion

XXD can improve the spatial learning and memory ability of SAMP8， reduce the production and deposition of LPS， SAA and Aβ

1-42

in brain and intestine， and increase the content of ACH. The mechanism of its prevention and treatment of AD maybe related to regulating intestinal microecology， affecting flora diversity and improving inflammatory response.

关键词

Keywords

references

常福厚，白图雅，吕晓丽，等 . 中蒙药对老年性痴呆治疗的研究进展［J］. 神经药理学报， 2018 ， 8 （ 2 ）： 61 - 62 .

SORIA LOPEZ JA ， GONZÁLEZ HM ， LÉGER GC . Alzheimer's disease ［J］. Handb Clin Neurol ， 2019 ， 167 ： 231 - 255 . doi： 10.1016/B978-0-12-804766-8.00013-3 http://dx.doi.org/10.1016/B978-0-12-804766-8.00013-3 .

MAYER EA ， NANCE K ， CHEN S . The gut-brain axis ［J］. Annu Rev Med ， 2022 ， 73 ： 439 - 453 . doi： 10.1146/annurev-med-042320-014032 http://dx.doi.org/10.1146/annurev-med-042320-014032 .

OSADCHIY V ， MARTIN CR ， MAYER EA . The gut-brain axis and the microbiome： mechanisms and clinical implications ［J］. Clin Gastroenterol Hepatol ， 2019 ， 17 （ 2 ）： 322 - 332 .

蔡泳昱，吴泳锡，李方彤，等 . 肠道菌群及其代谢产物与神经退行性疾病关系研究进展［J］. 应用化学， 2023 ， 40 （ 3 ）： 309 - 316 .

DOIFODE T ， GIRIDHARAN VV ， GENEROSO JS ， et al . The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology ［J］. Pharmacol Res ， 2021 ， 164 ： 105314 . doi： 10.1016/j.phrs.2020.105314 http://dx.doi.org/10.1016/j.phrs.2020.105314 .

第五永长 . 老年性痴呆“髓空痰浊”病机及治法再识［J］. 中医杂志， 2016 ， 57 （ 12 ）： 1075 - 1077 .

王德学 . 洗心汤治疗阿尔茨海默病36例疗效观察［J］. 中国民间疗法， 2016 ， 24 （ 2 ）： 46 - 47 .

张慧欣 . 洗心汤对AD模型大鼠神经炎症水平及肠道菌群的影响［D］. 咸阳：陕西中医药大学， 2022 .

王登坤，第五永长，苟于瑞，等 . 洗心汤对阿尔茨海默病模型大鼠海马BDNF、TrkB蛋白表达及肠道菌群多样性的影响［J］. 中医杂志， 2021 ， 62 （ 15 ）： 1362 - 1369 .

雷筱菁，第五永长 . 补益脾胃元气方药防治阿尔茨海默病的作用及相关机制研究进展［J］. 河北中医， 2018 ， 40 （ 7 ）： 1108 - 1112 .

黄继汉，黄晓晖，陈志扬，等 . 药理试验中动物间和动物与人体间的等效剂量换算［J］. 中国临床药理学与治疗学， 2004 ， 9 （ 9 ）： 1069 - 1072 .

第五永长，田金洲，时晶 . 从清代名医陈士铎治疗痴呆学术特色谈脾脑相关［J］. 四川中医， 2011 ， 29 （ 2 ）： 43 - 44 .

LIU B ， LIU J ， SHI JS . SAMP8 mice as a model of age-related cognition decline with underlying mechanisms in Alzheimer's disease ［J］. J Alzheimers Dis ， 2020 ， 75 （ 2 ）： 385 - 395 .

ABOUELASRAR SS ， GOUWY M ， VAN DAMME J ， et al . The turning away of serum amyloid a biological activities and receptor usage ［J］. Immunology ， 2021 ， 163 （ 2 ）： 115 - 127 .

程妍，第五永长，丁鸿莉，等 . 洗心汤对肠上皮屏障炎症模型P-gp/eCBs轴的影响［J］. 中国中医药信息杂志， 2023 ， 30 （ 4 ）： 88 - 93 .

BOWMAN GL ， DAYON L ， KIRKLAND R ， et al . Blood-brain barrier breakdown， neuroinflammation， and cognitive decline in older adults ［J］. Alzheimers Dement ， 2018 ， 14 （ 12 ）： 1640 - 1650 .

BAIRAMIAN D ， SHA S ， ROLHION N ， et al . Microbiota in neuroinflammation and synaptic dysfunction： a focus on Alzheimer's disease ［J］. Mol Neurodegener ， 2022 ， 17 （ 1 ）： 19 .

HUSTON JM . The vagus nerve and the inflammatory reflex： wandering on a new treatment paradigm for systemic inflammation and sepsis ［J］. Surg Infect （Larchmt）， 2012 ， 13 （ 4 ）： 187 - 193 .

TACKENBERG C ， NITSCH RM . The secreted APP ectodomain sAPPα， but not sAPPβ， protects neurons against Aβ oligomer-induced dendritic spine loss and increased tau phosphorylation ［J］. Molecular Brain ， 2019 ， 12 （ 1 ）： 27 .

BHATTACHARJEE S ， LUKIW WJ . Alzheimer's disease and the microbiome ［J］. Front Cell Neurosci ， 2013 ， 7 ： 153 . doi： 10.3389/fncel.2013.00153. eCollection 2013 http://dx.doi.org/10.3389/fncel.2013.00153.eCollection2013 .

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Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice

DOI：10.13288/j.11-2166/r.2023.24.013

摘要

Abstract

关键词

Keywords

references

Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ_1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice