Effect of <italic style="font-style: italic">Bushen Yisui Formula</italic> （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice

ZHANG Xinning; CHEN Zhigang; CHEN Lu; KANG Shenghua

doi:10.13288/j.11-2166/r.2023.01.013

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Effect of Bushen Yisui Formula （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice

更新时间：2022-12-29

- Effect of Bushen Yisui Formula （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice
- Journal of Traditional Chinese Medicine Vol. 64, Issue 1, Pages: 71-76(2023)
- 作者机构：
  
  1.北京中医药大学，北京市朝阳区北三环东路11号，100029
  2.北京中医药大学东方医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.01.013
  CLC：
- Received：04 May 2022，
  
  Revised：2022-07-15，
  
  Published：02 January 2023
- 稿件说明：
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张新宁,陈志刚,陈路等.补肾益髓方对帕金森病模型小鼠脑组织NLRP3炎症小体激活相关蛋白表达的影响[J].中医杂志,2023,64(01):71-76.

ZHANG Xinning,CHEN Zhigang,CHEN Lu,et al.Effect of Bushen Yisui Formula （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(01):71-76.
张新宁,陈志刚,陈路等.补肾益髓方对帕金森病模型小鼠脑组织NLRP3炎症小体激活相关蛋白表达的影响[J].中医杂志,2023,64(01):71-76. DOI： 10.13288/j.11-2166/r.2023.01.013.

ZHANG Xinning,CHEN Zhigang,CHEN Lu,et al.Effect of Bushen Yisui Formula （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2023,64(01):71-76. DOI： 10.13288/j.11-2166/r.2023.01.013.

摘要

目的

观察补肾益髓方对帕金森病（PD）模型小鼠运动症状的影响并探讨其可能的作用机制。

方法

34只C57BL/6J小鼠随机选取10只作为正常组，其余24只予MPTP 溶液30 mg/（kg·d）连续5天腹腔注射制备PD模型，将造模成功的24只小鼠随机分为模型组和补肾益髓方组各12只。补肾益髓方组小鼠予补肾益髓方配方颗粒水溶液（浓度0.22 g/ml）0.1 ml/10 g灌胃，正常组及模型组小鼠予等体积生理盐水灌胃，各组均每天1次，连续14天。各组小鼠采用转棒疲劳试验进行行为学评价，尼氏染色观察中脑黑质纹状体病理学形态，免疫组化检测中脑黑质纹状体酪氨酸羟化酶（TH）阳性细胞表达，Western Blot法检测小鼠脑组织NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体激活相关蛋白［包括NLRP3、半胱氨酸天冬氨酸蛋白酶1（Caspase-1）、信号转接凋亡相关斑点样蛋白（ASC）、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）］表达。

结果

与正常组比较，模型组小鼠在转棒上停留时间显著缩短，中脑黑质纹状体TH阳性细胞表达减少，脑组织中IL-1β、TNF-α、NLRP3、ASC、Caspase-1蛋白表达升高（

＜0.01）；尼氏染色结果显示，模型组小鼠黑质纹状体区神经元减少、萎缩、紊乱，胞体变小，尼氏小体减少。与模型组比较，补肾益髓方组小鼠转棒上停留时间延长，黑质纹状体TH阳性细胞表达增多，脑组织中IL-1β、TNF-α、NLRP3、ASC、Caspase-1蛋白表达下降（

＜0.05）；尼氏染色结果显示，补肾益髓方组小鼠黑质纹状体区大部分神经元细胞结构完备，核固缩、破裂现象减少，尼氏小体数量增多。

结论

补肾益髓方可改善PD的运动症状，其作用机制可能与调节NLRP3炎症小体介导的细胞焦亡有关。

Abstract

Objective

To observe the effects of

Bushen Yisui Formula

（补肾益髓方， BYF） on motor symptoms of Parkinson's disease （PD） model mice， and to explore its possible mechanism.

Methods

Ten out of 34 C57BL/6J mice were randomly selected as the normal group， and the remaining 24 mice were injected intraperitoneally with 30 mg/（kg·d） of MPTP solution for 5 consecutive days to make the PD model. Then， the 24 successfully modeled mice were randomly divided into model group and BYF group with 12 mice in each group. The mice in the BYF group was given intragastric administration of 0.1 ml/10 g of BYF granules solution at concentration of 0.22 g/ml， and those in the normal group and model group were given equal amount of normal saline by intragastric administration， once a day for 14 consecutive days. The rotarod performance test was performed for behavioral evaluation. The pathological morphology of the substantia nigra striatum was observed through Nisch staining， and the expression of tyrosine hydroxylase （TH） positive cells in the substantia nigra striatum was detected by immunohistochemistry. The expression of NOD-like receptor thermoprotein domain-associated protein 3 （NLRP3） inflammasome activation-related proteins， including NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were detected by western blotting.

Results

Compared to those in the normal group， the residence time on the rotating rod in the model group was significantly shortened， and the expression of TH-positive cells in midbrain substantia nigra striatum was reduced， while the expressions of IL-1β， TNF-α， NLRP3， ASC and Caspase-1 in brain tissue increased （

＜0.01）. Nishi staining showed that the neurons in the substantia nigra striatum area of mice in the model group were reduced， atrophy and disordered， with smaller cell body and reduced Nishi body than those in the normal group. Compared to those in the model group， the residence time on the rotating rod in BYF group was prolonged， and the expression of TH-positive cells in the substania nigra striatum increased， while the expressions of IL-1β， TNF-α， NLRP3， ASC and Caspase-1 in brain tissue decreased （

＜0.05）. The results of Nishi staining showed that the structure of most neurons in the substantia nigra striatum area of the BYF group was complete， and the nucleolysis and rupture were reduced， with increased number of Nishi bodies than those in the model group.

Conclusion

BYF can improve the motor symptoms of PD， and its mechanism may be related to the regulation of NLRP3 inflammasome mediated pyroptosis.

关键词

Keywords

references

TOLOSA E ， GARRIDO A ， SCHOLZ SW ， et al . Challenges in the diagnosis of Parkinson's disease ［J］. Lancet Neurol ， 2021 ， 20 （ 5 ）： 385 - 397 .

QI S ， YIN P ， WANG L ， et al . Prevalence of Parkinson's disease： a community-based study in China ［J］. Mov Disord ， 2021 ， 36 （ 12 ）： 2940 - 2944 .

YOU H ， MARIANI LL ， MANGONE G ， et al . Molecular basis of dopamine replacement therapy and its side effects in Parkinson's disease ［J］. Cell Tissue Res ， 2018 ， 373 （ 1 ）： 111 - 135 .

梁慧荟，王凯华，陈真珍 . 帕金森病的中医治疗进展［J］. 广西中医药， 2020 ， 43 （ 5 ）： 62 - 65 .

陈路，陈志刚，侯月 . 滋肾益髓方治疗帕金森病运动及非运动症状的疗效观察［J］. 北京中医药大学学报， 2014 ， 37 （ 3 ）： 209 - 212 .

ADAMS B ， NUNES JM ， PAGE MJ ， et al . Parkinson's disease： a systemic inflammatory disease accompanied by bacterial inflammagens ［J］. Front Aging Neurosci ， 2019 ， 11 ： 210 . doi： 10.3389/fnagi.2019.00210 http://dx.doi.org/10.3389/fnagi.2019.00210 .

AHMED S ， KWATRA M ， RANJAN PS ， et al . Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease ［J］. Brain Behav Immun ， 2021 ， 91 ： 142 - 158 . doi： 10.1016/j.bbi. 2020.09.017 http://dx.doi.org/10.1016/j.bbi.2020.09.017 .

WANG S ， YUAN YH ， CHEN NH ， et al . The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson's disease ［J］. Int Immunopharmacol ， 2019 ， 67 ： 458 - 464 . doi： 10.1016/j.intimp. 2018. 12.019 http://dx.doi.org/10.1016/j.intimp.2018.12.019 .

ZHANG QS ， HENG Y ， MOU Z ， et al . Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease ［J］. Acta Pharmacol Sin ， 2017 ， 38 （ 10 ）： 1317 - 1328 .

陶计委，南亚强，周杰，等 . Exendin-4通过抑制Toll样受体4/核因子κB信号通路对帕金森病小鼠保护作用的研究［J］. 中国病理生理杂志， 2022 ， 38 （ 3 ）： 502 - 508 .

魏伟，吴希美，李元建 . 药理实验方法学［M］. 北京：人民卫生出版社： 69- 74 .

POEWE W ， SEPPI K ， TANNER CM ， et al . Parkinson's disease ［J］. Nat Rev Dis Primers ， 2017 ， 3 ： 17013 . doi： 10.1038/nrdp.2017.13 http://dx.doi.org/10.1038/nrdp.2017.13 .

伊宏煜，王涛，谷孙泽栋，等 . 细胞焦亡与临床疾病及其相关信号通路［J］. 中国免疫学杂志， 2019 ， 35 （ 16 ）： 2038 - 2042 .

PANICKER N ， KANTHASAMY A ， KANTHASAMY AG . Fyn amplifies NLRP3 inflammasome signaling in Parkinson's disease ［J］. Aging （Albany NY）， 2019 ， 11 （ 16 ）： 5871 - 5873 .

CODOLO G ， PLOTEGHER N ， POZZOBON T ， et al . Triggering of inflammasome by aggregated alpha-synuclein， an inflammatory response in synucleinopathies ［J］. PLoS One ， 2013 ， 8 （ 1 ）： e55375 . doi： 10.1371/journal.pone. 0055375 http://dx.doi.org/10.1371/journal.pone.0055375 .

CHENG J ， LIAO Y ， DONG Y ， et al . Microglial auto-phagy defect causes parkinson disease-like symptoms by accelerating inflammasome activation in mice ［J］. Autophagy ， 2020 ， 16 （ 12 ）： 2193 - 2205 .

GORDON R ， ALBORNOZ EA ， CHRISTIE DC ， et al . Inflammasome inhibition prevents alpha-synuclein patho-logy and dopaminergic neurodegeneration in mice ［J］. Sci Transl Med ， 2018 ， 10 （ 465 ）： eaah4066 . doi： 10. 1126/scitranslmed.aah4066 http://dx.doi.org/10.1126/scitranslmed.aah4066 .

HAQUE ME ， AKTHER M ， JAKARIA M ， et al . Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease ［J］. Mov Disord ， 2020 ， 35 （ 1 ）： 20 - 33 .

许燕娟，陈映君，郑春叶，等 . 明清医家论治颤证学术思想探讨［J］. 中医药学报， 2021 ， 49 （ 5 ）： 65 - 69 .

陈路，韦一佛，刘明，等 . 补肾益髓法对帕金森病肾虚髓减证患者非运动症状的影响［J］. 中医杂志， 2019 ， 60 （ 3 ）： 229 - 231 .

韦一佛，陈路，高燕洁，等 . 应用帕金森病中医生存质量量表评价滋肾益髓方辅助治疗帕金森病髓海不足证临床疗效［J］. 中医杂志， 2018 ， 59 （ 8 ）： 672 - 676 .

齐月，黄金泳，张子炜，等 . MPTP诱导的帕金森病小鼠模型表型特点［J］. 神经解剖学杂志， 2022 ， 38 （ 1 ）： 107 - 110 .

冯建军，郭雄 . 银杏叶提取物对帕金森病模型大鼠神经形态学的影响［J］. 西部医学， 2013 ， 25 （ 10 ）： 1455 - 1457 .

ROOSTALU U ， SALINAS C ， THORBEK DD ， et al . Quantitative whole-brain 3D imaging of tyrosine hydroxylase-labeled neuron architecture in the mouse MPTP model of Parkinson's disease ［J］. Dis Model Mech ， 2019 ， 12 （ 11 ）： dmm042200 . doi： 10.1242/dmm.042200 http://dx.doi.org/10.1242/dmm.042200 .

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Effect of Bushen Yisui Formula （补肾益髓方） on the Expression of NLRP3 Inflammasome Activation-related Protein in the Brain Tissue in Parkinson's Disease Model Mice

DOI：10.13288/j.11-2166/r.2023.01.013

摘要

Abstract

关键词

Keywords

references