Anterior|Siguiente

Impacto de Heixiaoyao en la inflamación neuronal en ratones APP/PS1 y la vía de señalización NLRP3/Caspase-1/GSDMD

  • role： First author第一作者
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

    Xichang Hospital of TCM，Xichang 615000，China

  • Email：543767241@qq.com
  • Introduction：周君，硕士，医师，从事中医复方物质基础及作用机制研究，E-mail：543767241@qq.com
ZHOU Jun12,  
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

    Qujing 69 Hospital，China RongTong Medical Healthcare Group Co.， Ltd.， Qujing 655000，China

LI Mingcheng13,  
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

    Xingtai Hospital of TCM，Xingtai 054000，China

LYU Yujie14,  
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

    Zhengzhou TCM Hospital Affiliated to Henan University of Chinese Medicine，Zhengzhou 450007，China

MENG Zhipeng15,  
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

    Guizhou Health Vocational College，Tongren 554300，China

HU Yunyun16,  
  • role： Corresponding author通信作者
  • Affiliation：

    Gansu Engineering Laboratory for New Products of Traditional Chinese Medicine （TCM）， Gansu Key Laboratory of TCM Excavation and Innovative Transformation，Gansu University of Chinese Medicine，Lanzhou 730000，China

  • Email：whp@gszy.edu.cn
  • Introduction：王虎平，博士，教授，博士生导师，从事中医复方物质基础及作用机制研究，Tel：0931-5162454，E-mail：whp@gszy.edu.cn
WANG Huping1*

resumen

El objetivo de este estudio es observar el impacto del medicamento Heixiaoyao en la capacidad de aprendizaje y memoria en ratones modelo de la enfermedad de Alzheimer, y estudiar su mecanismo de acción a través del análisis de la vía de señalización NLRP3 / Caspase-1 / GSDMD, que interviene en la respuesta inflamatoria del sistema nervioso. Los ratones APP / PS1 (4 meses) se dividieron en grupo modelo, grupo MCC950 y grupos de dosis alta, media y baja, y se utilizaron ratones C57BL / 6J como grupo de control. Después de 7 días de adaptación, cada grupo de ratones recibió una intervención individual: las dosis alta, media y baja del medicamento se administraron por vía oral (25,79, 12,90, 6,45 g·kg-1·d-1) dos veces al día. Al grupo MCC950 se le administró una inyección subcutánea (10 mg·kg-1·2 d-1), y al grupo de control se le administró una cantidad equivalente de solución salina fisiológica por vía oral. Después de 90 días de intervención, se probó la capacidad de aprendizaje y memoria utilizando el laberinto de agua Y y la prueba de natación de Morris, y la estructura de las neuronas en el hipocampo se observó con hematoxilina-eosina (HE), el nivel de expresión de la proteína precursora de amiloide (APP) en la región CA3 del hipocampo se determinó mediante inmunohistoquímica, así como el nivel de expresión de interleucinas (IL) -10, IL-18, IL-1β en el tejido hippocampal se determinó mediante ELISA, y el nivel de expresión de proteínas tóxicas (NLRP3, Caspase-1, GSDMD, GSDMD-N) en el tejido hippocampal y la detección de la expresión conjunta de GSDMD-N y la proteína de unión al calcio iónico Iba-1 usando inmunotinción, inmunofluorescencia y Western blot se determinaron. Los resultados mostraron que Heixiaoyao puede influir en la liberación de factores inflamatorios regulando la vía de señalización NLRP3/Caspase-1/GSDMD, y así atenuar la inflamación del sistema nervioso, mejorar los cambios patológicos del tejido del hipocampo y los trastornos de aprendizaje y memoria para el tratamiento de la enfermedad de Alzheimer.

palabra clave

Enfermedad de Alzheimer; Heixiaoyao; neuroinflamación; vía de señalización NLRP3/Caspase-1 / GSDMD; Estudio experimental

References

  1. 1.
    WANG Y Q，LIANG J H，JIA R X，et al.Alzheimer disease in China（2015-2050） estimated using the 1% population sampling survey in 2015［J］.China J AD Relat Disord，2019，2（1）：289-298.
  2. 2.
    HAMPEL H，CARACI F，CUELLO A C，et al.A path toward precision medicine for neuroinflammatory mechanisms in Alzheimer's disease［J］.Front Immunol，2020，11：456.
  3. 3.
    YANG C S，WU H Y，LI H L，et al.Effects of HeiXiaoYao powder on the behavior and the TNF-α，IL-6 and IL-1β contents of Alzheimer disease rat models［J］.West J Tradit Chin Med，2015，（2）：10-12
  4. 4.
    MA C L，WU H Y，LAN M H，et al.Effect of Heixiaoyao Powder on expressions of genes and proteins related to Aβ degradation in hippocampus of APP/PSⅠ double transgenic mice［J］.Chin Arch Tradit Chin Med，2020，38（3）：115-118.
  5. 5.
    LI M C，ZHOU J，HU Y Y，et al.Heixiaoyao powder interferes with microglia polarization in AD model mice by regulating NOX2/ROS/NF-κB signaling pathway［J］.China J Chin Mater Med，2023，48（15）：4027-4038.
  6. 6.
    KINNEY J W，BEMILLER S M，MURTISHAW A S，et al.Inflammation as a central mechanism in Alzheimer's disease［J］.Alzheimers Dement（NY），2018，4：575-590.
  7. 7.
    LIU W Q，LIU H，YANG J Y，et al.Aβ deposition in the brain of APP/PS1 transgenic mice causes learning and memory impairment by causing neurons loss and inhibiting cell proliferation of CA3 and CA1 regions［J］.Pract Pharm Clin Remed，2020，23（5）：385-390.
  8. 8.
    WATAMURA N，SATO K，SAIDO T C.Mouse models of Alzheimer's disease for preclinical research［J］.Neurochem Int，2022，158：105361.
  9. 9.
    PAN H Y，ZHANG N，ZHOU Y，et al.The effect of MCC950 on NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury in rats［J］.Chin J New Drugs Clin Rem，2022，41（12）：754-758.
  10. 10.
    STANCU I C，CREMERS N，VANRUSSELT H，et al.Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo［J］.Acta Neuropathol，2019，137（4）：599-617.
  11. 11.
    SONG C W，DAI X L，JIANG Z F.Research advances in experimental animal models of Alzheimer's disease［J］.J Biol，2013，30（5）：85-88.
  12. 12.
    WEST M J，COLEMAN P D，FLOOD D G，et al.Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease［J］.Lancet，1994，344（8925）：769-772.
  13. 13.
    LUČIŪNAITĖ A，MCMANUS R M，JANKUNEC M，et al.Soluble Aβ oligomers and protofibrils induce NLRP3 inflammasome activation in microglia［J］.J Neurochem，2020，155（6）：650-661.
  14. 14.
    LEONG Y Q，NG K Y，CHYE S M，et al.Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death［J］.Metab Brain Dis，2020，35（1）：11-30.
  15. 15.
    CALDWELL J H，KLEVANSKI M，SAAR M，et al.Roles of the amyloid precursor protein family in the peripheral nervous system［J］.Mech Dev，2013，130（6-8）：433-446.
  16. 16.
    GOTOH N，SAITO Y，HATA S，et al.Amyloidogenic processing of amyloid β protein precursor（APP） is enhanced in the brains of alcadein α-deficient mice［J］.J Biol Chem，2020，295（28）：9650-9662.
  17. 17.
    BEYREUTHER K，MASTERS C L.Amyloid precursor protein（APP） and beta A4 amyloid in the etiology of Alzheimer's disease：Precursor-product relationships in the derangement of neuronal function［J］.Brain Pathol，1991，1（4）：241-251.
  18. 18.
    MIGLIORINI P，ITALIANI P，PRATESI F，et al.The IL-1 family cytokines and receptors in autoimmune diseases［J］.Autoimmun Rev，2020，19（9）：102617.
  19. 19.
    XIA S，ZHANG Z，MAGUPALLI V G，et al.Gasdermin D pore structure reveals preferential release of mature interleukin-1［J］.Nature，2021，593（7860）：607-611.
  20. 20.
    HAN X，XU T，FANG Q，et al.Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy［J］.Redox Biol，2021，44：102010.
  21. 21.
    LYU Y.NLRP-3/Caspase-1/GSDMD axis mediated microglia pyroptosis-A new pathway for hypoxic-ischemic brain damage［D］.Suzhou：Soochow University，2020.
  22. 22.
    CHEN Y Q， YANG J， PEI W L， et al. Hei Xiaoyaosan modulates oxidative stress and apoptosis to exert neuroprotective effect in Alzheimer's disease rats［J］.Chin J Exp Tradit Med Form，2025，doi：.
  23. 23.
    CHEN K L，LI H Q，WANG Q L，et al.Research progress on neuroinflammatory biomarkers in Alzheimer's disease［J］.Chin J Lab Diagn，2023，27（1）：89-92.
  24. 24.
    WANG H P， YANG J， CHEN Y Q. Hei Xiaoyaosan improves learning and memory abilities in Alzheimer's disease by regulating cell apoptosis［J］.Chin J Exp Tradit Med Form，2025，doi：.
  25. 25.
    YANG J， CHEN Y Q， PEI W L， et al.Hei Xiaoyaosan inhibits ferroptosis by regulating SIRT1/p53/SLC7A11 signaling pathway to ameliorate cognitive dysfunction in rat model of Alzheimer's disease［J］.Chin J Exp Tradit Med Form，2025，doi：.
  26. 26.
    MAGALHÃES C A，CARVALHO M，SOUSA L P，et al.Alzheimer's disease and cytokine IL-10 gene polymorphisms：Is there an association？［J］.Arq Neuropsiquiatr，2017，75（9）：649-656.
  27. 27.
    TENNAKOON A，KATHARESAN V，MUSGRAVE I F，et al.Normal aging，motor neurone disease，and Alzheimer's disease are characterized by cortical changes in inflammatory cytokines［J］.J Neurosci Res，2022，100（2）：653-669.
  28. 28.
    WESTON L L，JIANG S，CHISHOLM D，et al.Interleukin-10 deficiency exacerbates inflammation-induced tau pathology［J］.J Neuroinflammation，2021，18（1）：161.
  29. 29.
    BAI H，ZHANG Q.Activation of NLRP3 inflammasome and onset of Alzheimer's disease［J］.Front Immunol，2021，12：701282.
  30. 30.
    HENEKA M T，KUMMER M P，STUTZ A，et al.NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice［J］.Nature，2013，493（7434）：674-678.
  31. 31.
    DEMPSEY C，RUBIO ARAIZ A，BRYSON K J，et al.Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice［J］.Brain Behav Immun，2017，61：306-316.
  32. 32.
    WANG L J，LI K，GAO J，et al.Study on the effect of trans-cinnamaldehyde on improving memory impairment by inhibiting IL-1β in prefrontal cortex of mice with Alzheimer's disease［J］.World Sci Technol-Mod Tradit Chin Med，2021，23（2）：429-436.
  33. 33.
    PELLEGRINI C，FORNAI M，ANTONIOLI L，et al.Phytochemicals as novel therapeutic strategies for NLRP3 inflammasome-related neurological，metabolic，and inflammatory diseases［J］.Int J Mol Sci，2019，20（12）：2876.

Leer el texto completo

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website