二精丸对去卵巢＋<italic style="font-style: italic">D</italic>-半乳糖联合A<italic style="font-style: italic">β</italic><sub>1-40</sub>所致肾阴虚AD大鼠海马蛋白质组学的影响

黄丽萍; 杨喜洋; 燕波; 邱小鹏; 严斐霞; 孙梦盛; 谢永艳; 官扬; 周茂福; 陈耀辉

doi:10.13422/j.cnki.syfjx.20200637

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二精丸对去卵巢＋D-半乳糖联合Aβ_1-40所致肾阴虚AD大鼠海马蛋白质组学的影响

经典名方 | 更新时间：2021-02-09

- 二精丸对去卵巢＋D-半乳糖联合Aβ_1-40所致肾阴虚AD大鼠海马蛋白质组学的影响
- Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ_1-40
- 中国实验方剂学杂志 2020年26卷第9期页码：15-22
- 作者机构：
  
  1.江西中医药大学　药学院　科技学院，南昌　 330004
  2.江西省人民医院，南昌　 330006
- 作者简介：
  
  [第一作者]　黄丽萍，博士，教授，从事中药精神神经药理学的研究，E-mail：jxnchlp@163.com
  *陈耀辉，硕士，副主任医师，从事肾病临床与实验研究，E-mail：yhchendoc@163.com
- 基金信息：
  
  江西省自然科学基金项目(20171BAB205083);江西省主要学科学术和技术带头人项目(20182BCB22005);江西省卫计委中医药科研计划项目(2016A023);江西省研究生创新专项(YC2017-S356)
- DOI：10.13422/j.cnki.syfjx.20200637
  中图分类号： R2-0; R289; R285.5
- 收稿日期：2019-10-29，
  
  网络出版日期：2019-12-07，
  
  纸质出版日期：2020-05-05
- 稿件说明：
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黄丽萍, 杨喜洋, 燕波, 等. 二精丸对去卵巢＋D-半乳糖联合Aβ_1-40所致肾阴虚AD大鼠海马蛋白质组学的影响[J]. 中国实验方剂学杂志, 2020,26(9):15-22.

Li-ping HUANG, Xi-yang YANG, Bo YAN, et al. Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ_1-40[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 15-22.
黄丽萍, 杨喜洋, 燕波, 等. 二精丸对去卵巢＋D-半乳糖联合Aβ_1-40所致肾阴虚AD大鼠海马蛋白质组学的影响[J]. 中国实验方剂学杂志, 2020,26(9):15-22. DOI： 10.13422/j.cnki.syfjx.20200637.

Li-ping HUANG, Xi-yang YANG, Bo YAN, et al. Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ_1-40[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 15-22. DOI： 10.13422/j.cnki.syfjx.20200637.

摘要

目的：

探究二精丸对去卵巢＋

-半乳糖联合

-淀粉样蛋白

1-40

)所致肾阴虚阿尔茨海默病(AD)大鼠生物学基础的影响。

方法：

大鼠去卵巢后随机分为5组，即模型组、多奈哌齐组、二精丸高、中、低剂量组，每组11只，另设11只为假手术组，术后1周，连续腹腔注射

-半乳糖7周，术后4周，单侧海马注射A

1-40

。术后3周开始灌胃给药，模型组与假手术组灌胃生理盐水，二精丸高、中、低剂量组分别用对应浓度灌胃给药(9.0，4.5，2.25 g·kg

-1

)，多奈哌齐组灌胃1.0 mg·kg

-1

多奈哌齐，给药体积为10 mL·kg

-1

，每日1次，连续给药35 d。给药第31天，Y迷宫检测大鼠学习能力。末次给药后麻醉大鼠，分离大鼠海马，尼氏染色观察形态学。提取海马蛋白，Nanol-ESI液相-质谱联用系统检测蛋白，Protein Discovery软件鉴定蛋白，SIEVE软件对海马蛋白进行相对定量定性分析，PANTHER Classification System数据库对差异蛋白进行基因本体(GO)分析，String分析和京都基因与基因组百科全书(KEGG)富集信号通路。

结果：

与模型组大鼠比较，二精丸高、中剂量组大鼠Y迷宫正确交替率明显提高(

0.05)，海马CA1区神经元数量明显提高(

0.01)；二精丸高剂量组的差异蛋白(Ratio

1.5或Ratio

0.5)有胰岛素样生长因子-1受体(IGF-1R)等115个，中剂量组差异蛋白有突触素等94个，多奈哌齐组差异蛋白有乙酰辅酶A乙酰转移酶等87个。GO分析发现这些蛋白主要分为微管相关蛋白、热休克蛋白、能量代谢相关蛋白等与AD相关蛋白；KEGG分析发现上述差异蛋白共涉及Dopaminergic synaps等93条信号通路。

结论：

二精丸可能是通过磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号通路、胰岛素信号通路、酸活化蛋白激酶(AMPK)信号通路、雌激素信号通路，Dopaminergic synapse等多条通路相关蛋白的表达，从而达到防治肾阴虚AD的目的。

Abstract

Objective:

To explore the effect of Erjingwan on the biological basis of kidney yin deficiency Alzheimer' s disease(AD)rats induced by ovariectomy+

-galactose combined with amyloid beta

1-40

Method:

After ovariectomy

rats were randomly divided into five groups: model group

positive group

Erjingwan high

medium and low dose group

11 rats in each group

and 11 rats in sham operation group. One week after operation

-galactose was injected intraperitoneally for 7 weeks

and four weeks after operation

1-40

was injected unilaterally into hippocampus. The rats in model group and sham-operation group were given saline by intragastric administration 3 weeks after operation. The rats in high

middle and low dose groups of Erjingwan were given corresponding concentration (9.0

4.5

2.25 g·kg

-1

). The rats in positive control group were given Donepezil 1.0 mg·kg

-1

with dosage of 10 mL·kg

-1

once a day for 35 consecutive days. After 30 days of administration

the learning ability of the rats were examined using a Y-maze. The hippocampus tissues of rats were isolated. The morphology of hippocampus was observed by Nissl staining.The proteins were detected by Nanol-ESI liquid-mass spectrometry system and identified by protein Discovery software. Relative quantitative and qualitative analysis of differential proteins in hippocampus was performed by SIEVE software

and Gene Ontology of differential protein was performed by PANTHER Classification System database. String analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed on the differential proteins.

Result:

Compared with model group

the correct rate of Y maze in the high and middle dose groups of Erjingwan was significantly raised(

0.05)

and the number of neurons in the hippocampal CA1 area was significantly increased(

0.01).115 differential proteins (Ratio

1.5 or Ratio

0.5) such as Insulin-like growth factor 1 receptors(IGF-1R) were found in the high-dose group of the Erjingwan group as well as 94 differential proteins such as Synaptophysin expressed in the middle-dose group of the Erjingwan. And there are 87 differential proteins such as Acetyl-CoA acetyltransferase-cytosolic in the positive drug group. It showed that these proteins were mainly divided into tubule-related proteins

heat shock proteins

energy metabolism-related proteins and AD-related proteins with GO analysis. It was found that the above differential proteins involved 93 signaling pathways such as Dopaminergic synaps by KEGG analysis.

Conclusion:

Erjingwan can improve cognitive impairment and neuronal damage in rats with kidney yin deficiency

possibly by altering the expression of multiple pathway-associated proteins such as phosphatidylinositol 3-kinase/protein kinase B signaling pathway(PI3K/Akt)

insulin signaling pathway

and adenylate-activated protein kinase (AMPK)signaling pathway

estrogen signaling pathway

and Dopaminergic synapse.

关键词

Keywords

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二精丸对去卵巢＋D-半乳糖联合Aβ1-40所致肾阴虚AD大鼠海马蛋白质组学的影响

Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ1-40

DOI：10.13422/j.cnki.syfjx.20200637

摘要

Abstract

关键词

Keywords

references

二精丸对去卵巢＋D-半乳糖联合Aβ_1-40所致肾阴虚AD大鼠海马蛋白质组学的影响

Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ_1-40