Effect of Tongmai Kaiqiao Pills on Mitochondrial Biogenesis of Hippocampal Neurons in Rats with Vascular Cognitive Impairment Based on AMPK/PGC-1α Signaling Pathway

  • role: First author第一作者
  • Affiliation:

    School of Rehabilitation Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China

  • Email:819931585@qq.com
  • Introduction:马璐瑶,在读硕士,从事神经系统疾病损伤后功能障碍的康复治疗研究,E-mail:819931585@qq.com
MA Luyao1,  
  • role: Corresponding author通信作者
  • Affiliation:

    Henan Province Hospital of Traditional Chinese Medicine,Zhengzhou 450053,China

  • Email:yanjieli2008@126.com
  • Introduction:李彦杰,硕士,主任医师,硕士生导师,从事中西医结合治疗神经系统疾病研究,Tel:0371-60908747,E-mail:yanjieli2008@126.com
LI Yanjie2*,  
  • Affiliation:

    School of Rehabilitation Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China

LIU Haoyuan1,  
  • Affiliation:

    The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,China

BAI Yanjie3,  
  • Affiliation:

    Henan Province Hospital of Traditional Chinese Medicine,Zhengzhou 450053,China

XING Ruoxing2

resumen

El objetivo de la investigación es observar el efecto de las tabletas de desbloqueo de las vías arteriales en la activación de la proteína AMP (AMPK) / activador subunitario γ PGC-1α (PGC-1α) y el efecto sobre la biogénesis mitocondrial, para estudiar el mecanismo potencial de mejora del déficit cognitivo en ratas con infarto cerebral (VCI) y acelerar su mejora. Se seleccionaron 12 ratas machos de entre 72 ratas, 12 de ellas fueron elegidas para someterse a una operación ficticia y las ratas restantes se sometieron a una operación mejorada a 2VO; las ratas exitosas fueron divididas en un grupo modelo, un grupo de dosis alta y un grupo de dosis baja (27.6 y 13.8 g / kg), un grupo combinado (27.6 g / kg de tabletas para desbloqueo de vías + Dorsomorfina 25 mg / kg), con 4 semanas de inyecciones intraabdominales repetidas del medicamento apropiado, utilizando la prueba del laberinto acuático de Morris para probar la capacidad de aprendizaje y memoria de las ratas. Se utilizó una tinción especial en hematoxilina y eosina (HE) para evaluar los cambios histológicos en el hipocampo de las ratas; se utilizó un método de dosificación de trifosfato de adenosina (ATP) para probar los tejidos cerebrales. El nivel de oxígeno activo celular en los tejidos cerebrales fue evaluado utilizando la prueba MitoSOX Red para detectar el nivel de oxígeno activo celular (ROS) en las ratas; el número de copias de ADN mitocondrial (mtDNA) fue probado utilizando la reacción en cadena de la polimerasa en tiempo real (PCR en tiempo real) con precisión cuántica de fluorescencia; se utilizó la microscopía electrónica de transmisión (TEM) para observar los cambios patológicos de las mitocondrias; el nivel de proteínas fue probado utilizando una prueba de inmunotintado (Western blot) en las ratas en los tejidos cerebrales para evaluar las cantidades de proteínas AMPK y PGC-1α

palabra clave

Tongmai Kaiqiao pills;vascular cognitive impairment;mitochondrial biogenesis;AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) signaling pathway

References

  1. 1.
    GONG T,LUO Z,HUANG L,et al.Effect and mechanism of Yisui Fuyongtang (YSFYT) decoction on cognitive function and synaptic plasticity in rats with vascular cognitive impairment[J].J Immunol Res,2022,2022:1709360.
  2. 2.
    RUNDEK T,TOLEA M,ARIKO T,et al.Vascular Cognitive Impairment (VCI)[J].Neurotherapeutics,2022,19 (1):68-88.
  3. 3.
    LI H,WANG L.Progress in pathophysiological mechanisms of vascular cognitive impairment[J]. Chin J Pathophysiol,2021,37(2):363-368.
  4. 4.
    YUAN Y,TIAN Y,JIANG H,et al. Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia- reperfusion injury[J].Front Mol Neurosci,2023,16:1224964.
  5. 5.
    GONG M,JIA J.Rutaecarpine mitigates cognitive impairment by balancing mitochondrial function through activation of the AMPK/PGC1α pathway[J].Mol Neurobiol,2023,60(11):6598-6612.
  6. 6.
    ABU SHELBAYEH O ,ARROUM T,MORRIS S,et al.PGC-1α is a master regulator of mitochondrial lifecycle and ROS stress response[J].Antioxidants (Basel),2023,12 (5):1075.
  7. 7.
    SZALARDY L,MOLNAR M,TOROK R,et al.Lack of age-related clinical progression in PGC-1α-deficient mice - implications for mitochondrial encephalopathies[J].Behav Brain Res,2016,313:272-281.
  8. 8.
    DING H M,LI Y J,QIN H W,et al.Mechanistic study of Tongmai Kaiqiao pill in the treatment of vascular dementia in rats based on HIF-1α/BNIP3 signaling pathway regulating mitochondrial autophagy[J].Chin J Exp Tradit Med Form,2024,30(21):52-60.
  9. 9.
    ZHAO N N, LI Y J,QIN H W,et al.Changes in ferroptosis in hippocampal neurons of vascular dementia model rats treated with Tongmai Kaiqiao pill[J].Chin J Tissue Eng Res,2025,29(7):1401-1407.
  10. 10.
    LI X Q,AI J C,LIU Q,et al.Studies on the mechanism of Zhifuxin on vascular cognitive impairment[J].J Chin Med Mater,2018,41(1):175-179.
  11. 11.
    CHEN Y F,QU M,ZHANG J,et al.Treatment of vascular dementia from blood collaterals and Qi collaterals based on collateral disease theory[J].World Chin Med,2024,19(9):1276-1278,1285.
  12. 12.
    WANG F M,LIU B,GAI P P, et al. A clinical study on Shouwu Yizhi formula combined with cognitive rehabilitation train-ing in the treatment of vascular cognitive impairment. [J]. Clin J Chin Med,2023,15(30):68-72.
  13. 13.
    ZHANG J,TAO X J,MA X W,et al.The research progress on treating vascular dementia from the perspective of Zang-Fu theory[J].Hubei J Tradit Chin Med,2024,46(1):59-63.
  14. 14.
    LU W W,GUO Y K.Systematic evaluation and Meta-analysis of the efficacy and safety of Buyang Huanwu decoction in the treatment of vascular cognitive impairment[J].World Chin Med,2022,17(8):1095-1100.
  15. 15.
    ZHANG M,BAI Y J,SHEN X,et al.Ma Yunzhi's experience in the treatment of vascular dementia by tonifying the kidney and detoxifying[J].Jilin J Chin Med,2022,42(8):895-899.
  16. 16.
    LIU L J,CAI H B,WANG J J,et al.Correlation between cognitive dysfunction and TCM syndromes(phlegm,stagnation and deficiency)in vascular cognitive impairment[J].Chin Archives Trad Chin Med,2019, 37(11):2686-2689.
  17. 17.
    ZHU G W,ZHU R L,LI X M,The impact of Yangxue Yizhi Tang combined with acupuncture at the Four Shencong points on mild cognitive impairment after cerebral infarction[J].TCM Res,2024,37(9):52-55.
  18. 18.
    LI Y Y,WANG X Q,LI C J,et al.Effect of Buyang Huanwu decoction combined with operation therapy on shoulder—hand syndrome after stroke and its effect on upper limb motor function[J].Chin Archives Trad Chin Mede,2021,39(6):192-195
  19. 19.
    QU P,LUO L M,XU L,et al.Effects of Chaihu Shugan powder modified with jiangxiangru on intestinal inflammation and gut microbiota in obese and depressed rats[J].Pharmacol Clin Chin Mater Med,2023,39(11):9-17.
  20. 20.
    HU Y F,WANG X,LIU Q,et al.Research progress of chinese medicine Fushen[J].J Liaoning Univ Tradit Chin Med,2023,25(1):115-121.
  21. 21.
    LI D D,CHEN J.Research progress of Tongqiao Huoxue decoction in treatment of vascular cognitive impairment and dementia[J].Chin Archives Tradit Chin Med,2024,42(10):103-108.
  22. 22.
    DUNCOMBE J,KITAMURA A,HASE Y,et al.Chronic cerebral hypoperfusion:A key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia[J].Clin Sci (Lond),2017,131 (19):2451-2468.
  23. 23.
    OGNJANOVSKI N,SCHAEFFER S,WU J,et al. Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation[J].Nat Commun,2017,8:15039.
  24. 24.
    LEVIT A,HACHINSKI V,WHITEHEAD S N.Neurovascular unit dysregulation, white matter disease, and executive dysfunction: The shared triad of vascular cognitive impairment and Alzheimer disease[J].Geroscience,2020,42 (2):445-465.
  25. 25.
    BATTLE C E,ABDUL-RAHIM A H,SHENKIN S D,et al.Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: A network Meta-analysis[J].Cochrane Database Syst Rev,2021,2 (2):CD013306.
  26. 26.
    SUN C,LIU M,LIU J,et al.Shenma Yizhi decoction improves the mitochondrial structure in the brain and ameliorates cognitive impairment in VCI rats via the AMPK/UCP2 signaling pathway[J].Neuropsychiatr Dis Treat,2021,17:1937-1951.
  27. 27.
    KIM E,PARK M,JEONG J,et al.Cholinesterase inhibitor donepezil increases mitochondrial biogenesis through AMP-activated protein kinase in the hippocampus[J].Neuropsychobiology,2016,73 (2):81-91.
  28. 28.
    JORNAYVAZ F R,SHULMAN G I.Regulation of mitochondrial biogenesis[J].Essays Biochem,2010,47:69-84.
  29. 29.
    PALIKARAS K,TAVERNARAKIS N.Mitochondrial homeostasis:The interplay between mitophagy and mitochondrial biogenesis[J].Exp Gerontol,2014,56:182-188.
  30. 30.
    YAN Y,ZHOU X E,XU H E,et al.Structure and physiological regulation of AMPK[J].Int J Mol Sci,2018,19 (11):3534.
  31. 31.
    JIANG S,LI T,JI T,et al.AMPK:Potential therapeutic target for ischemic stroke[J].Theranostics,2018,8 (16):4535-4551.
  32. 32.
    LI P A,HOU X,HAO S.Mitochondrial biogenesis in neurodegeneration[J].J Neurosci Res,2017,95 (10):2025-2029.
  33. 33.
    ZHANG S,WU X,WANG J,et al.Adiponectin/AdiopR1 signaling prevents mitochondrial dysfunction and oxidative injury after traumatic brain injury in a SIRT3 dependent manner[J].Redox Biol,2022,54:102390
  34. 34.
    LI L,XIAO L,HOU Y,et al.Sestrin2 silencing exacerbates cerebral ischemia/reperfusion injury by decreasing mitochondrial biogenesis through the AMPK/PGC-1α pathway in rats[J].Sci Rep,2016,6:30272.
  35. 35.
    HAN B,JIANG W,LIU H,et al.Upregulation of neuronal PGC-1α ameliorates cognitive impairment induced by chronic cerebral hypoperfusion[J].Theranostics,2020,10 (6):2832-2848.
  36. 36.
    CHEN S D,LIN T K,LIN J W,et al.Activation of calcium/calmodulin-dependent protein kinase Ⅳ and peroxisome proliferator-activated receptor γ coactivator-1α signaling pathway protects against neuronal injury and promotes mitochondrial biogenesis in the hippocampal CA1 subfield after transient global ischemia[J].J Neurosci Res,2010,88 (14):3144-3154.

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