Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and A<italic style="font-style: italic">β</italic> Clearance in Mice Model of Alzheimer's Disease

LIU Jing; CHEN Kang; ZHOU Yushun; ZHANG Zhezuo; YU Guran; LI Hao

doi:10.13422/j.cnki.syfjx.20241636

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Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and Aβ Clearance in Mice Model of Alzheimer's Disease

更新时间：2025-03-06

- Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and Aβ Clearance in Mice Model of Alzheimer's Disease
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 31, Issue 7, Pages: 43-52(2025)
- 作者机构：
  
  1.南京中医药大学附属医院，南京 210029
  2.中国中医科学院望京医院，北京 100102
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20241636
  CLC： R259;R285;R742
- Received：17 July 2024，
  
  Accepted：18 September 2024，
  
  Online First：23 September 2024，
  
  Published：05 April 2025
- 稿件说明：
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刘晶,陈康,周渝顺等.参芎黄连解毒汤对阿尔茨海默病模型小鼠神经元损伤和Aβ清除的影响[J].中国实验方剂学杂志,2025,31(07):43-52.

LIU Jing,CHEN Kang,ZHOU Yushun,et al.Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and Aβ Clearance in Mice Model of Alzheimer's Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(07):43-52.
刘晶,陈康,周渝顺等.参芎黄连解毒汤对阿尔茨海默病模型小鼠神经元损伤和Aβ清除的影响[J].中国实验方剂学杂志,2025,31(07):43-52. DOI： 10.13422/j.cnki.syfjx.20241636.

LIU Jing,CHEN Kang,ZHOU Yushun,et al.Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and Aβ Clearance in Mice Model of Alzheimer's Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(07):43-52. DOI： 10.13422/j.cnki.syfjx.20241636.

摘要

目的

研究参芎黄连解毒汤对阿尔茨海默病（AD）模型小鼠

淀粉样蛋白（A

）清除能

力和神经元损伤的影响。

方法

选取36只2月龄SPF级C57BL/6J小鼠为实验对象，利用双侧海马区注射A

寡聚体的方式构建阿尔茨海默病模型小鼠，设置空白组、假手术组、参芎黄连解毒汤（中药）低、高剂量组（3.27、6.54 g·kg

-1

）和多奈哌齐组（0.65 mg·kg

-1

）。采用水迷宫和旷场实验评价小鼠的学习记忆能力和活动功能，苏木素-伊红（HE）和尼氏染色法观察脑组织病理，活体成像评估荧光A

经脑脊液的代谢情况，离子钙结合衔接分子-1（Iba-1）染色观察小胶质细胞活化情况，免疫荧光和酶联免疫吸附测定法检测脑组织和血清中神经营养因子-3（NT-3）和脑源性神经营养因子（BDNF）含量，蛋白免疫印迹法（Western blot）检测海马组织中炎症和通路蛋白的表达。

结果

与空白组、假手术组比较，模型组小鼠逃避潜伏期延长，平台停留时间缩短，海马组织出现神经元固缩，尼氏体溶解、小胶质细胞活化等病理表现，荧光A

经脑脊液代谢速度减慢，海马组织BDNF、NT-3、白细胞介素-10（IL-10）表达水平显著降低（

0.01）；海马组织肿瘤坏死因子-

（TNF-

）、白细胞介素-6（IL-6）、白细胞介素-1

（IL-1

）、Toll样受体4（TLR4）、髓样分化因子88（MyD88）和磷酸化核转录因子-

B（p-NF-

B p65）表达水平明显升高（

0.05，

0.01）；与模型组比较，中药低、高剂量组和多奈哌齐组小鼠逃避潜伏期缩短，平台停留时间延长；海马组织神经元核固缩、尼氏体溶解、小胶质细胞活化等情况好转，荧光A

经脑脊液代谢增快，海马组织中BDNF、NT-3表达增多（

0.01），TLR4、MyD88、p-NF-

B p65表达显著降低（

0.05，

0.01）；中药高剂量组海马组织TNF-

明显降低（

0.05），IL-10表达明显升高（

0.05）；多奈哌齐组海马组织TNF-

、IL-6、IL-1

的表达明显降低（

0.05，

0.01）。

结论

参芎黄连解毒能改善AD小鼠神经元损伤，增强脑脊液流动，从而促进A

的清除，改善小鼠的学习记忆功能，其机制可能与抑制小胶质细胞活化、抗炎和调控TLR4/MyD88/NF-

B通路相关。

Abstract

Objective

To investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid

-protein （A

） and neuronal damage in the mouse model of Alzheimer's disease （AD）.

Methods

A total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of A

oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg

-1

， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg

-1

） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally，

in vivo

imaging was employed to measure the metabolism of fluorescent A

in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue.

Results

Compared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent A

through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （

0.01）. The expression levels of tumor necrosis factor-

（TNF-

）， interleukin-6 （IL-6）， interleukin-1

（IL-1

）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-

B （p-NF-

B p65） in hippocampus were significantly increased （

0.05，

0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence A

was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （

0.01）， and the expression of TLR4， MyD88 and p-NF-

B p65 was significantly decreased （

0.05，

0.01）. The expression of TNF-

in the hippocampus of the high-dose group was significantly decreased （

0.05）， and the expression of IL-10 was significantly increased （

0.05）. The expression of TNF-

， IL-6 and IL-1

in the hippocampus of the donepezil group was significantly decreased （

0.05，

0.01）.

Conclusion

Shenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of A

and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-

B signaling pathway.

关键词

Keywords

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Effect of Shenxiong Huanglian Jiedu Decoction on Neuronal Damage and Aβ Clearance in Mice Model of Alzheimer's Disease

DOI：10.13422/j.cnki.syfjx.20241636

摘要

Abstract

关键词

Keywords

references