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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：文胤琏，在读硕士，从事脑缺血机制及中药干预研究，E-mail：wenyinlian11@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：刘欣，博士，教授，从事脑缺血机制及中药干预研究，E-mail：liuxin1011@bucm.edu.cn
LIU Xin*

resumen

El objetivo del estudio fue investigar los mecanismos de acción de las cápsulas cerebrales en la inhibición de la contracción celular perivascular inducida por la ruta RHOA/ROCK1 en el daño por reperfusión de isquemia cerebral en ratas. Se dividieron 90 ratas al azar en un grupo de cirugía falsa, un grupo modelo, un grupo de extracto de ginkgo biloba (21.6 mg/kg-1), y grupos de dosis baja, media y alta de cápsulas cerebrales (55, 110, 220 mg/kg-1), con 15 ratas en cada grupo. Adaptaron los bloqueos temporales de la arteria cerebral media (tMCAO) en todos los grupos excepto el de cirugía falsa. Se utilizó la evaluación de la función nerviosa y el láser de dispersión de flujo sanguíneo para la imagen de la circulación sanguínea cerebral, la técnica de tinción con tetrazolio de cloruro (TTC) para calcular la tasa de infarto cerebral, las técnicas de tinción de Heidenhain-Earle (HE) y de Nissl para estudiar los cambios patológicos, la microscopía electrónica para observar la morfología de las células perivasculares, la tinción de azul de Evans para la observación del daño de la barrera hematoencefálica, el kit para medir los niveles de albúmina, y los niveles de albúmina modificados por isquemia. Se utilizaron técnicas de PCR cuantitativo en tiempo real (qPCR) y Western blot para medir los niveles de expresión de ARNm y proteínas de RHOA, ROCK1, receptor del factor de crecimiento derivado de plaquetas β (PDGFRB), α-actina de músculo liso (α-SMA), proteína de unión estrecha-1 (ZO-1), metaloproteinasa-2 de matriz (MMP-2), y metaloproteinasa-9 de matriz (MMP-9). En comparación con el grupo de cirugía falsa, las ratas en el grupo modelo mostraron una disminución en la puntuación de la función nerviosa, un porcentaje de disminución en el flujo sanguíneo cerebral, un aumento en la tasa de infarto cerebral (P<0.01), contracción nuclear neuronal cortical y edema, una reducción en el número de células de Nissl y el área perivascular, un incremento en el contenido de albúmina en la corteza (P<0.05), un aumento en los niveles de albúmina modificada por isquemia (P<0.01), un aumento relativo en los niveles de ARNm y proteínas de RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, y MMP-9 (P<0.01), y una disminución en los niveles de ZO-1. En comparación con el grupo modelo, las ratas en cada grupo tratado mostraron una mejora en la puntuación de la función nerviosa, una disminución en el porcentaje de descenso del flujo sanguíneo cerebral, y una reducción en la tasa de infarto cerebral (P<0.01). También mostraron reducción en los cambios patológicos en la corteza, un incremento en el número de células de Nissl y el área perivascular, una reducción en el contenido de albúmina (P<0.01), una disminución en los niveles de albúmina modificada por isquemia (P<0.01), una disminución en los niveles relat

palabra clave

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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