Effect and mechanism of <italic style="font-style: italic">Shouwu</italic> Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats

ZHANG Chao; JIA Xiufeng; HUANG Wanling; ZHOU Yong; TANG Qi; CHEN Gang

doi:10.3969/j.issn.1006-2157.2023.01.012

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Effect and mechanism of Shouwu Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats

Experimental Studies | 更新时间：2023-02-03

- Effect and mechanism of Shouwu Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 1, Pages: 65-76(2023)
- 作者机构：
  
  1.湖北中医药大学基础医学院　武汉　430065
  2.湖北中医药高等专科学校中医系
  3.武汉市中医医院
  4.湖北省中医院
- 作者简介：
  
  Prof.CHEN Gang, Ph.D., Doctoral Supervisor, No. 4, Huayuanshan, Wuchang District, Wuhan. E-mail: 250149875@qq.com
- 基金信息：
  
  The Second Medical Leading Talents Project of Hubei Province and the Project of Director of Hubei Famous Doctors Studio(鄂卫通〔2019〕47号);Key Scientific Research Project of the Health and Family Planning Commission of Hubei Province on the Integration of Traditional Chinese and Western Medicine(鄂卫生计生通〔2017〕20号);Young Talents Projectof Chinese Medicine Research Project of Hubei Provincial Health and Health Commission(ZY2021Q031);Hubei Provincial Health Commission General Key Project(WJ2019H422)
- DOI：10.3969/j.issn.1006-2157.2023.01.012
  CLC： R285.5
- Received：26 July 2022，
  
  Online First：20 October 2022，
  
  Published：30 January 2023
- 稿件说明：
移动端阅览
ZHANG Chao, JIA Xiufeng, HUANG Wanling, et al. Effect and mechanism of Shouwu Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(1): 65-76. DOI: 10.3969/j.issn.1006-2157.2023.01.012.
DOI：

ZHANG Chao, JIA Xiufeng, HUANG Wanling, et al. Effect and mechanism of Shouwu Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(1): 65-76. DOI: 10.3969/j.issn.1006-2157.2023.01.012. DOI：

摘要

目的

探讨首乌丸延缓脑衰老的可能作用机制。

方法

将SPF级SD雄性大鼠50只任意分为正常组、模型组、维生素E组、首乌丸组及首乌丸2倍剂量组。除正常组外，其余4组均用D－半乳糖(120 mg/kg)复制衰老模型，同时首乌丸组和首乌丸2倍剂量组分别予首乌丸1.08、2.16 g/kg灌胃，维生素E组予维生素E 0.018 g/kg灌胃。6周造模结束后，各组任意选取6只小鼠进行16S rRNA测序分析肠道菌群多样性和物种丰度的变化，检测海马β－半乳糖苷酶活力，苏木素－伊红(HE)染色观察空肠组织病理形态学变化，用酶联免疫吸附(ELISA)法检测各组大鼠血清及海马的氧化三甲胺(TMAO)含量。Spearman相关性分析基于属水平的差异菌群与血清TMAO的相关性。

结果

与正常组相比，模型组海马β－半乳糖苷酶活性上升(

0.01)；与模型组相比，首乌丸组和首乌丸2倍剂量组海马β－半乳糖苷酶活性下降(

0.01)。与模型组相比，首乌丸组和首乌丸2倍剂量组回肠纹状缘比较整齐，黏膜上皮细胞脱落减少。与正常组相比，模型组Chao1指数、Faith指数、Observed_otus指数下降(

0.05，

0.01)；与模型组相比，首乌丸组Chao1指数、Faith指数、Observed_otus指数、Shannon指数上升(

0.05，

0.01)，首乌丸2倍剂量组Chao1指数、Shannon指数上升(

0.05)。肠道菌群Beta多样性分析，各组样本能够区分。门水平肠道菌群，与正常组相比，模型组拟杆菌门、放线菌门相对丰度下降(

0.01)，变形菌门、蓝藻菌门相对丰度上升(

0.01)；与模型组相比，首乌丸组和首乌丸2倍剂量组放线菌门丰度升高(

0.01)，蓝藻菌门丰度降低(

0.01)，厚壁菌门与拟杆菌门相对丰度的比率均降低。属水平，与正常组相比，模型组普雷沃菌属、乳酸杆菌属、颤螺菌属、拟杆菌属、副雷沃菌属相对丰度下降(

0.01)；与模型组相比，经首乌丸干预后，普雷沃菌属、乳酸杆菌属、颤螺菌属、拟杆菌属、副雷沃菌属、布劳特菌属、狄氏副拟杆菌属相对丰度均上升(

0.01)。与正常组相比，模型组血清及海马TMAO含量升高(

0.01)；与模型组相比，首乌丸组和首乌丸2倍剂量组血清及海马TMAO含量下降(

0.01)。Spearman相关性分析提示，普雷沃菌属、乳酸杆菌属、副雷沃菌属、布劳特菌属相对丰度与血清TMAO含量呈负相关。

结论

首乌丸能够降低D－半乳糖衰老大鼠海马β－半乳糖苷酶活性，改善空肠病理形态，其作用机制可能是通过调节肠道菌群，减少TMAO的生成，进而延缓脑衰老。

Abstract

Objective

To explore the possible mechanism of

Shouwu

Pill in delaying brain aging.

Methods

Fifty male SPF SD rats were randomly divided into the normal group

model group

vitamin E group

Shouwu

Pill group

and double dose

Shouwu

Pill group. Except the normal group

the other four groups were used to generate aging models with D-galactose (120 mg/kg). Simultaneously

Shouwu

Pill was used to intervene the

Shouwu

Pill group and double dose

Shouwu

Pill group (1.08

2.16 g/kg)

while the vitamin E group (0.018 g/kg) was given vitamin E by gavage. After 6 weeks of modeling

six mice per group were randomly selected for 16S rRNA sequencing to analyze the changes in intestinal flora diversity and species richness

and to detect the hippocampus β-galactosidase activity. Hematoxylin and eosin (HE) staining were used to observe the pathological changes of jejunum tissue

and the content of trimethylamine oxide (TMAO) in serum and hippocampus of rats in each group was detected by enzyme-linked immunosorbent assay (ELISA).

Results

Compared to the normal group

the β-galactosidase activity increased in the hippocampus of the model group(

0.01). Compared to the model group

the β-galactosidase activity decreased in the hippocampus of the

Shouwu

Pill group and double dose

Shouwu

Pill group(

0.01). Compared to the model group

the striated border of the ileum in the

Shouwu

Pill group and double dose

Shouwu

Pills group was neat

and the shedding of mucosal epithelial cells was reduced. Compared to the normal group

the model group showed a decreased Chao1 index

Faith index

and Observed_ otus (

0.05

0.01). Compared to the model group

the Chao1 index

Faith index

Observed_ otus

and Shannon index (

0.05

0.01) increased in the

Shouwu

Pill group

and the Chao1 index and Shannon index in the double dose group increased (

0.05). Beta diversity analysis of intestinal flora demonstrated that each group of samples could be significantly distinguished. At the phyla level

compared to the normal group

the abundance of Bacteroides and Actinomycetes in the model group decreased (

0.01)

while the abundance of Proteus and Cyanobacteria in the model group increased (

0.01). Compared to the model group

the ratio of relative abundance of Firmicutes and Bacteroides in the

Shouwu

Pill group and double dose

Shouwu

Pill group decreased

the abundance of Actinomycetes increased (

0.01)

and the abundance of Cyanobacteria decreased (

0.01). At the genus level

compared to the normal group

the relative abundance of

Prevotella

Lactobacillus

Vibrio

Bacteroides

and

Para Prevotella

in the model group decreased (

0.01). Compared to the model group

after the intervention of

Shouwu

Pill

the relative abundance of

Prevotella

Lactobacillus

Vibrio

Bacteroides

Para Prevotella

Brautzia

and

Para Prevotella

increased (

0.01). Compared to the normal group

the content of TMAO in the serum and hippocampus of the model group was significantly increased (

0.01). Compared to the model group

the content of TMAO in the serum and hippocampus in the

Shouwu

Pill group and double dose

Shouwu

Pill group were significantly decreased (

0.01). Spearman correlation analysis showed that

Prevotella

Lactobacillus

Parapre votella

and

Brautzia

were negatively correlated with serum TMAO.

Conclusion

Shouwu

Pill can reduce the β-galactosidase activity in the hippocampus of aging rats treated with D-galactose. Moreover

the β-galactosidase activity can improve the pathological morphology of the jejunum

which may delay brain aging by regulating intestinal flora and reducing the production of TMAO.

关键词

Keywords

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⁰

Effect and mechanism of Shouwu Pill on regulating intestinal flora and delaying brain aging in D-galactose model rats

DOI：10.3969/j.issn.1006-2157.2023.01.012

摘要

Abstract

关键词

Keywords

references