Effect of <italic style="font-style: italic">Bushen Huoxue Granules</italic> （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice

CHEN Qi; WANG Peng; CHEN Yingfan; LI Shaodan; YANG Minghui

doi:10.13288/j.11-2166/r.2025.04.011

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Effect of Bushen Huoxue Granules （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice

更新时间：2025-02-18

- Effect of Bushen Huoxue Granules （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice
- Journal of Traditional Chinese Medicine Vol. 66, Issue 4, Pages: 390-398(2025)
- 作者机构：
  
  1.解放军总医院第六医学中心中医医学部，北京市海淀区阜成路6号，100048
  2.解放军医学院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.04.011
  CLC：
- Received：09 September 2024，
  
  Revised：2024-11-22，
  
  Published：17 February 2025
- 稿件说明：
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陈琦,王鹏,谌盈帆等.补肾活血颗粒对帕金森病模型小鼠大脑黑质Nrf2/NLRP3炎症小体轴的影响[J].中医杂志,2025,66(04):390-398.

CHEN Qi,WANG Peng,CHEN Yingfan,et al.Effect of Bushen Huoxue Granules （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(04):390-398.
陈琦,王鹏,谌盈帆等.补肾活血颗粒对帕金森病模型小鼠大脑黑质Nrf2/NLRP3炎症小体轴的影响[J].中医杂志,2025,66(04):390-398. DOI： 10.13288/j.11-2166/r.2025.04.011.

CHEN Qi,WANG Peng,CHEN Yingfan,et al.Effect of Bushen Huoxue Granules （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(04):390-398. DOI： 10.13288/j.11-2166/r.2025.04.011.

摘要

目的

从核因子E2相关因子2（Nrf2）/核苷酸结构域样受体蛋白3（NLRP3）炎症小体轴探讨补肾活血颗粒治疗帕金森病（PD）的可能作用机制。

方法

将84只雄性C57/BL 6小鼠随机分为空白组、模型组、美多芭组、富马酸二甲酯组及补肾活血颗粒低、中、高剂量组，每组12只。除空白组外其余各组小鼠采用腹腔注射浓度为30 mg/ml的1-甲基-4苯基-1

6-四氢吡啶（MPTP）诱导PD小鼠模型，空白组小鼠腹腔注射等量生理盐水，每天1次，连续7天。造模成功后，补肾活血颗粒低、中、高剂量组分别给予补肾活血颗粒1.5、3、6 g/（kg·d）灌胃，美多芭组给予美多芭片0.113 g/（kg·d）灌胃，富马酸二甲酯组给予富马酸二甲酯50 mg/（kg·d）灌胃，空白组和模型组给予10 ml/（kg·d）蒸馏水灌胃。各组均每天灌胃1次，连续14天。采用旷场试验（总路程、中央区总路程和平均速度）、转棒实验（在棒时间）、爬杆实验（爬杆时间）评估小鼠行为学改变；ELISA法检测各组小鼠血清白细胞介素1β（IL-1β）、白细胞介素18（IL-18）、髓过氧化物酶（MPO）水平；免疫组化法检测小鼠大脑黑质酪氨酸羟化酶（TH）表达；免疫荧光法检测大脑黑质α-突触核蛋白（α-syn）表达；蛋白印迹法检测各组小鼠大脑黑质Nrf2、NLRP3、天冬氨酸蛋白水解酶1（Caspase1）、α-syn蛋白水平；RT-PCR法检测各组小鼠黑质

Nrf2

、

NLRP3

、

Caspase1

mRNA表达。

结果

与空白组比较，模型组小鼠总路程、中央区总路程和平均速度下降，在棒时间缩短，爬杆时间延长，大脑黑质TH表达降低、α-syn表达升高，Nrf2蛋白及其mRNA表达降低，NLRP3、Caspase1蛋白及其mRNA表达升高，血清IL-1β、IL-18和MPO水平升高（

＜0.05）。与模型组比较，各药物干预组上述指标均显著改善（

＜0.05）。与美多芭组比较，补肾活血颗粒高剂量组各指标差异均无统计学意义（

＞0.05）。与富马酸二甲酯组比较，补肾活血颗粒中、高剂量组黑质

Nrf2

mRNA表达升高（

＜0.05）。与补肾活血颗粒高剂量组比较，补肾活血颗粒低剂量组小鼠总路程、中央区总路程和平均速度下降，血清IL-18水平及大脑黑质α-syn、Nrf2、NLRP3、Cas

pase1蛋白水平降低，

Nrf2

mRNA表达亦降低（

＜0.05）。

结论

补肾活血颗粒治疗PD的机制可能通过激活大脑黑质Nrf2/NLRP3炎症小体轴，从而发挥减轻神经炎症和减少α-syn异常聚集的作用，且以高剂量组效果最好。

Abstract

Objective

To explore the possible mechanism of action of

Bushen Huoxue Granules

（补肾活血颗粒， BHG） in the treatment of Parkinson's disease （PD） through the Nrf2/NLRP3 inflammasome axis.

Methods

A total of 84 male C57/BL 6 mice were randomly divided into blank group， model group， Madopar group， dimethyl fumarate group， and low-， medium， and high-dose BHG group， with 12 mice in each group. Except for the blank group， all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1

6-tetrahydropyridine （MPTP） at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment， the low-， medium， and high-dose BHG groups were treated with 1.5， 3， and 6 g/（kg·d） of the BHG by gavage， respectively. The Madopar group was given 0.113 g/（kg·d） of Madopar tablets by gavage， and the dimethyl fumarate group was given 50 mg/（kg·d） of dimethyl fumarate solution. The blank group and the model group were given 10 ml/（kg·d） of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test （total distance， central area distance， and average speed）， rotarod test （time on the rod）， and climbing pole test （climbing time）. Serum levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and myeloperoxidase （MPO） were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase （TH） expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein （α-syn） expression. Western Blot was used to detect Nrf2， NLRP3， Caspase-1， and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expre

ssion levels of

Nrf2

，

NLRP3

， and

Caspase

in the brain substantia nigra.

Results

Compared with the blank group， the model group showed decreased total distance， central area distance， and average speed， reduced time on the rotarod， prolonged climbing time， reduced TH expression， increased α-syn expression， decreased Nrf2 protein and mRNA expression， increased NLRP3 and Caspase-1 protein and mRNA expression， and elevated serum IL-1β， IL-18， and MPO levels （

＜0.05）. Compared with the model group， all drug interventions significantly improved the above indicators （

＜0.05）. There was no significant differences in all indicators between the high-dose BHG group and the Madopar group （

＞0.05）. Compared with the dimethyl fumarate group， the medium and high-dose BHG groups showed increased

Nrf2

mRNA expression in the brain substantia nigra （

＜0.05）. Compared with the high-dose BHG group， the low-dose group showed decreased total distance， central area distance， and average speed， reduced serum IL-18 levels， decreased α-syn， Nrf2， NLRP3， and Caspase-1 protein levels， and lower

Nrf2

mRNA expression （

＜0.05）.

Conclusion

The mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra， thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.

关键词

Keywords

references

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Related Author

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Chinese People's Liberation Army Medical School

Department of Traditional Chinese medicine，The sixth medical center，The People's Liberation Army General Hospital

Graduate School，Beijing University of Chinese Medicine

Xiyuan Hospital，China Academy of Chinese Medical Sciences

School of Chinese Materia Medica， Shanghai University of Traditional Chinese Medicine

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Effect of Bushen Huoxue Granules （补肾活血颗粒） on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice

DOI：10.13288/j.11-2166/r.2025.04.011

摘要

Abstract

关键词

Keywords

references