Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway

  • role: First author第一作者
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

  • Email:wenyinlian11@bucm.edu.cn
  • Introduction:E-mailwenyinlian11@bucm.edu.cn
WEN Yinlian,  
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

SHANG Jinfeng,  
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

WANG Bohong,  
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

WEI Wanting,  
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

ZHANG Xiaolu,  
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

HUANG Guijinfeng,  
  • role: Corresponding author通信作者
  • Affiliation:

    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

  • Email:liuxin1011@bucm.edu.cn
  • Introduction:E-mailliuxin1011@bucm.edu.cn
LIU Xin*

Resümee

Das Ziel der Studie war es, die Mechanismen der Wirkung von Gehirnkapseln bei der Hemmung der perivaskulären Zellkontraktion, die durch den RHOA/ROCK1-Weg induziert wird, bei der Hirnischämie-Reperfusionsverletzung bei Ratten zu untersuchen. 90 Ratten wurden zufällig in eine Gruppe mit Placebo-Operation, eine Modellgruppe, eine Ginkgo-Biloba-Extrakt-Gruppe (21,6 mg/kg-1) und Gruppen mit niedriger, mittlerer und hoher Dosierung von Gehirnkapseln (55, 110, 220 mg/kg-1) mit jeweils 15 Ratten eingeteilt. Temporäre Blockierungen der mittleren Hirnarterie (tMCAO) wurden in allen Gruppen mit Ausnahme der Placebo-Operatiosgruppe verwendet. Es wurden die Bewertung der Nervenfunktion und der Laserblutsprühfluss für die zerebrale Blutflussbildgebung, die Chloridaldehyd-Triphenyltetrazoliumtetrachlorid (TTC)-Färbung zur Berechnung der Hirninfarkt-Rate, die Heidenhain-Earle (HE)- und Nissl-Färbung zur Untersuchung der pathologischen Veränderungen, die elektronenmikroskopische Untersuchung zur Beobachtung der Morphologie der perivaskulären Zellen, die Evans Blue-Färbung zur Beobachtung der Blut-Hirn-Schranke, die Messung des Albuminspiegels und des ischämisch modifizierten Albuminspiegels verwendet. Quantitative Echtzeit-Polymerase-Kettenreaktion (qPCR) und Western-Blot-Techniken wurden zur Messung der Expression von mRNA und Proteinen von RHOA, ROCK1, Plättchenabgeleitetem Wachstumsfaktorrezeptor β (PDGFRB), α-Glatte Muskel { α-SMA), Striate-Binding-Protein-1 (ZO-1), Matrixmetallopeptadase-2 (MMP-2) und Matrixmetallkurpelenase-9 (MMP-9) verwendet. Im Vergleich zur Placebogruppe zeigten die Ratten der Modellgruppe eine Verminderung der Nervenfunktionsbewertung, einen prozentualen Rückgang des zerebralen Blutflusses, eine Zunahme der Hirninfarktrate (P<0,01), kortikale Neuronenkernverdichtung und Schwellung, eine Verminderung der Anzahl der Nissl-Zellen und des perivaskulären Bereichs, ein Anstieg des Albumingehalts in der Rinde (P<0,05), eine Zunahme der ischämisch modifizierten Albuminspiegel (P<0,01), eine relative Zunahme der mRNA- und Protein Α -SMA, MMP-2 und MMP-9 (P<0,01) und eine verringerte ZO-1-Niveauerhöhung. Im Vergleich zur Model

Schlüsselwort

Naoxintong capsules;ischemia-reperfusion (I/R) injury;pericyte contraction;Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway;pharmacological mechanism

References

  1. 1.
    Report on Stroke Prevention and Treatment in China Writing Group.Brief report on stroke prevention and treatment in China,2021[J].Chin J Cerebrovasc Dis,2023,20(11):783-793.
  2. 2.
    LIM S,KIM T J,KIM Y J,et al.Senolytic therapy for cerebral ischemia-reperfusion injury[J].Int J Mol Sci,2021,22 (21):11967.
  3. 3.
    WOLLENWEBER F A,TIEDT S,ALEGIANI A,et al. Functional outcome following stroke thrombectomy in clinical practice[J].Stroke,2019,50 (9):2500-2506.
  4. 4.
    JIA M,JIN F,LI S,et al. No-reflow after stroke reperfusion therapy:An emerging phenomenon to be explored[J].Cns Neurosci Ther,2024,30 (2):e14631.
  5. 5.
    YUAN L,ZHANG X,WU J N,et al.Research progress of no-reflow phenomenon after revascularization in acute ischemic stroke[J].Chin J Clin Neurosci,2023,36(6):466-470.
  6. 6.
    SIMS D E. Diversity within pericytes[J].Clin Exp Pharmacol Physiol,2000,27 (10):842-846.
  7. 7.
    ZHANG Y,JIANG M,GAO Y,et al."No-reflow" phenomenon in acute ischemic stroke[J].J Cereb Blood Flow Metab,2024,44(1):19-37.
  8. 8.
    GARCÍA-QUINTANS N,SÁNCHEZ-RAMOS C,PRIETO I,et al. Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1Α-deficient mice[J].Angiogenesis,2016,19 (2):217-228.
  9. 9.
    SHI T F,ZHOU Z,JIANG W J,et al.Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway[J].Redox Rep,2024,29 (1):2382943.
  10. 10.
    DURHAM J T,SURKS H K,DULMOVITS B M,et al. Pericyte contractility controls endothelial cell cycle progression and sprouting:Insights into angiogenic switch mechanics[J].Am J Physiol Cell Physiol,2014,307 (9):C878-C892.
  11. 11.
    LI T S, YANG J, YANG C H. Pathogenesis of coronary NRP and TCM strategy in syndrome differentiation and treatment based on "collateral disease theory"[J].Acta Chin Med Pharmacol,2022,50(12):82-85.
  12. 12.
    XU J C,QIN Q J,SUN W M, et al.Exploration on dredging collateralsin traditional Chinese medicine and brain microcirculation dysfunction after cerebral infarction[J]. Liaoning J Tradit Chin Med,2021,48(1):78-80.
  13. 13.
    HUANG P J,HE A D,CHEN H Y.Curative effect of Naoxintong capsuless combined with metoprolol on arrhythmia of coronary heart disease and its effect on inflammatory factors[J].J New Chin Med,2023,55(21):24-28.
  14. 14.
    LIU X,WANG Q,CUI Y,et al.Multiple protein and mRNA expression correlations in the rat cerebral cortex after ischemic injury and repair due to Buchang Naoxintong Jiaonang (BNJ) intervention[J].Biomed Pharmacother,2020,doi:.
  15. 15.
    LONGA E Z,WEINSTEIN P R,CARLSON S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
  16. 16.
    WANG Z,DU X,YU D,et al. Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats[J].Eur J Histochem,2022,66(1):3328.
  17. 17.
    DENG K,COLLABORATORS G C O D.Global Burden of 288 Causes of Death And Life Expectancy Decomposition in 204 Countries and Territories and 811 Subnational Locations, 1990-2021:A systematic analysis for the global burden of disease study 2021[J].Lancet,2024,403 (10440):2100-2132.
  18. 18.
    RANDOLPH S A.Ischemic stroke[J].Workplace Health Saf,2016,64(9):444.
  19. 19.
    DANG C,LU J,SONG H Q,et al.Chinese expert consensus on clinical evaluation and treatment of ischemic penumbra in acute cerebral infarction[J].Chin J Nerv Ment Dis,2021,47(6):324-335.
  20. 20.
    HACKE W,KASTE M,BLUHMKI E,et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke[J].N Engl J Med,2008,359(13):1317-1329.
  21. 21.
    KLONER R A, KING K S, HARRINGTON M G. No-reflow phenomenon in the heart and brain[J].Am J Physiol Heart Circ Physiol,2018,315(3):H550-H562.
  22. 22.
    ZHANG S S,WANG J L.Discussion on syndrome differentiation and treatment of stroke from the perspective of latent toxin damaging defense, Qi,nutrient, and blood phases[J].Global Tradit Chin Med,2023,16(2):270-275.
  23. 23.
    LIU S, ZHANG Z X, KONG L B, et al. A principle-method-prescription-medicine system for no reflow after vascular recanalization in ischemic stroke based on the theory of vessels and collaterals in traditional Chinese medicine[J]. World Chin Med,2023,18(13):1834-1838.
  24. 24.
    LEI Y X, CHANG M L, WANG H H, et al. Naoxintong capsuless treat cardiac injury after cerebral ischemia via TLR2/TLR4 signaling pathway[J]. Chin J Exp Tradit Med Form,2023,29(24):104-112.
  25. 25.
    FAN S N. Intervention and mechanism of Qingkailing on pericytes morphology and function after cerebral infarction [D].Beijing:Beijing University of Chinese Medicine,2020.
  26. 26.
    METHNER C,MISHRA A,GOLGOTIU K,et al. Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis[J].Am J Physiol Heart Circ Physiol,2019,317 (2):H255-H263.
  27. 27.
    YEMISCI M,GURSOY-OZDEMIR Y,VURAL A,et al. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery[J].Nat Med,2009,15 (9):1031-1037.
  28. 28.
    KORTE N,ILKAN Z,PEARSON C L,et al.The Ca2+-gated channel tmem16a amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia[J].J Clin Invest,2022,132 (9):e154118.
  29. 29.
    LEE C H,AHN J H,LEE T K,et al. Comparison of neuronal death, blood-brain barrier leakage and inflammatory cytokine expression in the hippocampal CA1 region following mild and severe transient forebrain ischemia in gerbils[J].Neurochem Res,2021,46 (11):2852-2866.
  30. 30.
    LIDONG D,ZHANGHONG X,HUAWU M,et al. Ischemia modified albumin and miR-126 play important role in diagnosis of posterior circulation transient ischemic attack and prediction of secondary cerebral infarction[J].Neurol India,2021,69 (1):75-80.
  31. 31.
    STRATMAN A N,SCHWINDT A E,MALOTTE K M,et al. Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization[J].Blood,2010,116 (22):4720-4730.
  32. 32.
    GENOVÉ G,MOLLICK T,JOHANSSON K. Photoreceptor degeneration,structural remodeling and glial activation:A morphological study on a genetic mouse model for pericyte deficiency[J].Neuroscience,2014,279:269-284.
  33. 33.
    MACHIDA T,TAKATA F,MATSUMOTO J,et al. Brain pericytes are the most thrombin-sensitive matrix metalloproteinase-9-releasing cell type constituting the blood-brain barrier in vitro[J].Neurosci Lett,2015,599:109-114.
  34. 34.
    TAKAHASHI Y,MAKI T,LIANG A C,et al. p38 MAPKinase mediates transforming-growth factor-β1-induced upregulation of matrix metalloproteinase-9 but not -2 in human brain pericytes[J].Brain Res,2014,1593:1-8.
  35. 35.
    TAKATA F,DOHGU S,MATSUMOTO J,et al.Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro[J].J Neuroinflammation,2011,8:106.
  36. 36.
    SLADOJEVIC N,YU B,LIAO J K. ROCK as a therapeutic target for ischemic stroke[J].Expert Rev Neurother,2017,17 (12):1167-1177.
  37. 37.
    LU W,CHEN Z,WEN J.RhoA/ROCK signaling pathway and astrocytes in ischemic stroke[J].Metab Brain Dis,2021,36 (6):1101-1108.
  38. 38.
    ZHANG Y,MIAO L,PENG Q,et al.Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the Rhoa/Rock pathway[J].Phytomedicine,2022,105:154373.
  39. 39.
    RIKITAKE Y,KIM H H,HUANG Z,et al.Inhibition of Rho kinase (Rock) leads to increased cerebral blood flow and stroke protection[J].Stroke,2005,36 (10):2251-2257.
  40. 40.
    ALARCON-MARTINEZ L,YILMAZ-OZCAN S,YEMISCI M,et al.Retinal ischemia induces α-SMA-mediated capillary pericyte contraction coincident with perivascular glycogen depletion[J].Acta Neuropathol Commun,2019,7 (1):134.
  41. 41.
    O'FARRELL F M,ATTWELL D.A role for pericytes in coronary no-reflow[J].Nat Rev Cardiol,2014,11(7):427-432.
  42. 42.
    KOROL A,TAIYAB A,WEST-MAYS J A.RHOA/ROCK signaling regulates TGFB-induced epithelial-mesenchymal transition of lens epithelial cells through Mrtf-A[J].Mol Med,2016,22:713-723.

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