Volume 38 Issue 12
Dec.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Nanjing University of traditional Chinese Medicine  > 2022  >  38(12): 1128-1136
FENG Tao, LYU Yehua, WANG Sheng, HUANG Wei, MI Daguo. Neuroprotective Effect and Mechanism of Astragalus Injection on Acute Spinal Cord Injury in Rats[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(12): 1128-1136. doi: 10.14148/j.issn.1672-0482.2022.1128
Citation: FENG Tao, LYU Yehua, WANG Sheng, HUANG Wei, MI Daguo. Neuroprotective Effect and Mechanism of Astragalus Injection on Acute Spinal Cord Injury in Rats[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(12): 1128-1136. doi: 10.14148/j.issn.1672-0482.2022.1128
shu

Neuroprotective Effect and Mechanism of Astragalus Injection on Acute Spinal Cord Injury in Rats

doi: 10.14148/j.issn.1672-0482.2022.1128

  • Nantong Hospital of Traditional Chinese Medicine Affiliated to Nantong University, Nantong 226001, China

  • Received Date: 2021-11-08
    Available Online: 2022-12-15
    Abstract
  •   OBJECTIVE   To explore the neuroprotective function of Astragalus injection on acute spinal cord injury (SCI) in rats and its mechanism based on apoptosis signaling pathway.  METHODS   40 healthy male SD rats were randomly divided into sham operation group, SCI group, Astragalus injection low dose group (1 mL · kg-1), Astragalus injection medium dose group (2 mL · kg-1) and Astragalus injection high dose group (4 mL · kg-1). A modified heavy object method was used to construct an acute SCI rat model. The locomotor function of rats was evaluated according to BBB method and Rivlin inclined board test. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of spinal cord tissue. Nissl staining method was used to detect the degree of spinal cord neuronal cell damage. High-throughput transcriptome sequencing to analyze differentially expressed genes. The qPCR method verified the expression level of gene transcription. TUNEL kit was used to detect the apoptosis of spinal cord cells in each group. The expression levels of key proteins in the apoptosis pathway was detected by Western blot.  RESULTS   The results of BBB score and Rivlin plate test indicated that rats in the model group showed obvious motor dysfunction compared with the sham group. HE staining showed severe pathological changes in spinal cord tissue in the model group. Lighter Nissl staining showed severe neuronal cell damage in the model group. Compared with the sham group, 4 597 genes were differentially expressed in the spinal cord of the model group. The expressions of Fas, TRAIL, Caspase-3, Caspase-8, Caspase-9 and Bax proteins were significantly up-regulated (P < 0.01). Moreover, the protein expressions of Fas apoptosis inhibitor FAIM and anti-apoptotic factor Bcl-2 was significantly reduced (P < 0.01). Compared with the model group, the BBB score and the degree of Rivlin in the Astragalus injection group significantly increased and the degree of tissue lesions becomes smaller (P < 0.05, P < 0.01). As the dose of Astragalus injection increased, the degree of Nissl staining becomes deeper. The injury and apoptosis of spinal cord nerve cells in the Astragalus injection high dose group significantly alleviated (P < 0.01). Compared with the model group, the expressions of FAIM and TRAIL mRNA were significantly expressed in the high-dose Astragalus injection group (P < 0.01), the expressions of Fas, TRAIL, Caspase-3, Caspase-8, Caspase-9 and Bax protein in Astragalus injection groups were inhibited in a dose-dependent manner (P < 0.05, P < 0.01), the protein expressions of FAIM and Bcl-2 were up-regulated (P < 0.01).  CONCLUSION   Astragalus injection may inhibit the expressions of Fas and TRAIL proteins, thereby regulate the programmed apoptosis of neuronal cells, exert a neuroprotective effect on SCI, improve the degree of SCI, and accelerate the later neuromotor function recovery of obstacles.

     

    • FullText(HTML)
  • loading
    • References(33)
  • [1]
    KONG XY, GAO J. Macrophage polarization: A key event in the secondary phase of acute spinal cord injury[J]. J Cell Mol Med, 2017, 21(5): 941-954. doi: 10.1111/jcmm.13034
    [2]
    DIMITRIJEVIC MR, DANNER SM, MAYR W. Neurocontrol of movement in humans with spinal cord injury[J]. Artif Organs, 2015, 39(10): 823-833. doi: 10.1111/aor.12614
    [3]
    WANG HW, LIU XW, ZHAO YW, et al. Incidence and pattern of traumatic spinal fractures and associated spinal cord injury resulting from motor vehicle collisions in China over 11 years[J]. Medicine, 2016, 95(43): e5220. doi: 10.1097/MD.0000000000005220
    [4]
    WANG YL, YUAN YT, GAO YT, et al. MicroRNA-31 regulating apoptosis by mediating the phosphatidylinositol-3 kinase/protein kinase B signaling pathway in treatment of spinal cord injury[J]. Brain Dev, 2019, 41(8): 649-661. doi: 10.1016/j.braindev.2019.04.010
    [5]
    YANG R, GUO L, HUANG L, et al. Epidemiological characteristics of traumatic spinal cord injury in Guangdong, China[J]. Spine, 2017, 42(9): E555-E561. doi: 10.1097/BRS.0000000000001896
    [6]
    ALIZADEH A, DYCK SM, KARIMI-ABDOLREZAEE S. Traumatic spinal cord injury: An overview of pathophysiology, models and acute injury mechanisms[J]. Front Neurol, 2019, 10: 282. doi: 10.3389/fneur.2019.00282
    [7]
    ZHENG YJ, REN WY, ZHANG LN, et al. A review of the pharmacological action of Astragalus polysaccharide[J]. Front Pharmacol, 2020, 11: 349. doi: 10.3389/fphar.2020.00349
    [8]
    LUO YM, QIN Z, HONG Z, et al. Astragaloside Ⅳ protects against ischemic brain injury in a murine model of transient focal ischemia[J]. Neurosci Lett, 2004, 363(3): 218-223. doi: 10.1016/j.neulet.2004.03.036
    [9]
    WEI RD, LIU HD, CHEN R, et al. Astragaloside Ⅳ combating liver cirrhosis through the PI3K/Akt/mTOR signaling pathway[J]. Exp Ther Med, 2019, 17(1): 393-397.
    [10]
    ZHU JH, WEN K. Astragaloside Ⅳ inhibits TGF-β1-induced epithelial-mesenchymal transition through inhibition of the PI3K/Akt/NF-κB pathway in gastric cancer cells[J]. Phytother Res, 2018, 32(7): 1289-1296. doi: 10.1002/ptr.6057
    [11]
    LU WS, LI S, GUO WW, et al. Effects of astragaloside Ⅳ on diabetic nephropathy in rats[J]. Genet Mol Res, 2015, 14(2): 5427-5434. doi: 10.4238/2015.May.22.12
    [12]
    COSTA IM, LIMA FOV, FERNANDES LCB, et al. Astragaloside Ⅳ supplementation promotes a neuroprotective effect in experimental models of neurological disorders: A systematic review[J]. Curr Neuropharmacol, 2019, 17(7): 648-665. doi: 10.2174/1570159X16666180911123341
    [13]
    LIU GY, SONG JM, GUO YL, et al. Astragalus injection protects cerebral ischemic injury by inhibiting neuronal apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats[J]. Behav Brain Funct, 2013, 9: 36. doi: 10.1186/1744-9081-9-36
    [14]
    ZHOU LY, SONG ZF, ZHOU LW, et al. Protective role of Astragalus injection in spinal cord ischemia-reperfusion injury in rats[J]. Neurosciences, 2018, 23(2): 116-121. doi: 10.17712/nsj.2018.4.20170391
    [15]
    YUE RC, LI X, CHEN BY, et al. Astragaloside Ⅳ attenuates glutamate-induced neurotoxicity in PC12 cells through raf-MEK-ERK pathway[J]. PLoS ONE, 2015, 10(5): e0126603. doi: 10.1371/journal.pone.0126603
    [16]
    YIN F, ZHOU HF, FANG YC, et al. Astragaloside Ⅳ alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway[J]. J Ethnopharmacol, 2020, 248: 112319. doi: 10.1016/j.jep.2019.112319
    [17]
    YAO NW, LU Y, SHI LQ, et al. Neuroprotective effect of combining tanshinone ⅡA with low-dose methylprednisolone following acute spinal cord injury in rats[J]. Exp Ther Med, 2017, 13(5): 2193-2202. doi: 10.3892/etm.2017.4271
    [18]
    XU J, KIM GM, CHEN SW, et al. iNOS and nitrotyrosine expression after spinal cord injury[J]. J Neurotrauma, 2001, 18(5): 523-532. doi: 10.1089/089771501300227323
    [19]
    SINGH C, ROY-CHOWDHURI S. Quantitative real-time PCR: Recent advances[J]. Methods Mol Biol, 2016, 1392: 161-176.
    [20]
    KHORASANIZADEH M, YOUSEFIFARD M, ESKIAN M, et al. Neurological recovery following traumatic spinal cord injury: A systematic review and meta-analysis[J]. J Neurosurg Spine, 2019, 30(5): 683-699. doi: 10.3171/2018.10.SPINE18802
    [21]
    WANG HL, ZHOU QH, XU MB, et al. Astragaloside Ⅳ for experimental focal cerebral ischemia: Preclinical evidence and possible mechanisms[J]. Oxidat Med Cell Longev, 2017, 2017: 8424326.
    [22]
    XIA L, GUO DX, CHEN B. Neuroprotective effects of astragaloside Ⅳ on Parkinson disease models of mice and primary astrocytes[J]. Exp Ther Med, 2017, 14(6): 5569-5575.
    [23]
    LIN JL, PAN XX, HUANG CHONGAN, et al. Dual regulation of microglia and neurons by Astragaloside Ⅳ-mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury[J]. J Cell Mol Med, 2020, 24(1): 671-685. doi: 10.1111/jcmm.14776
    [24]
    OYINBO CA. Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade[J]. Acta Neurobiol Exp, 2011, 71(2): 281-299.
    [25]
    VON LEDEN RE, YAUGER YJ, KHAYRULLINA G, et al. Central nervous system injury and nicotinamide adenine dinucleotide phosphate oxidase: Oxidative stress and therapeutic targets[J]. J Neurotrauma, 2017, 34(4): 755-764. doi: 10.1089/neu.2016.4486
    [26]
    ZHANG Y, ZHANG Y, JIN XF, et al. The role of astragaloside Ⅳ against cerebral ischemia/reperfusion injury: Suppression of apoptosis via promotion of P62-LC3-autophagy[J]. Molecules, 2019, 24(9): 1838. doi: 10.3390/molecules24091838
    [27]
    BEATTIE MS, FAROOQUI AA, BRESNAHAN JC. Review of current evidence for apoptosis after spinal cord injury[J]. J Neurotrauma, 2000, 17(10): 915-925. doi: 10.1089/neu.2000.17.915
    [28]
    PRADELLI LA, BÉNÉTEAU M, RICCI JE. Mitochondrial control of caspase-dependent and-independent cell death[J]. Cell Mol Life Sci, 2010, 67(10): 1589-1597. doi: 10.1007/s00018-010-0285-y
    [29]
    KANTARI C, WALCZAK H. Caspase-8 and bid: Caught in the act between death receptors and mitochondria[J]. Biochim Biophys Acta BBA Mol Cell Res, 2011, 1813(4): 558-563. doi: 10.1016/j.bbamcr.2011.01.026
    [30]
    GALLUZZI L, BLOMGREN K, KROEMER G. Mitochondrial membrane permeabilization in neuronal injury[J]. Nat Rev Neurosci, 2009, 10(7): 481-494. doi: 10.1038/nrn2665
    [31]
    PLANELLS-FERRER L, URRESTI J, COCCIA E, et al. Fas apoptosis inhibitory molecules: More than death-receptor antagonists in the nervous system[J]. J Neurochem, 2016, 139(1): 11-21. doi: 10.1111/jnc.13729
    [32]
    SUREDA FX, JUNYENT F, VERDAGUER E, et al. Antiapoptotic drugs: A therapautic strategy for the prevention of neurodegenerative diseases[J]. Curr Pharm Des, 2011, 17(3): 230-245. doi: 10.2174/138161211795049732
    [33]
    HISATOMI T, ISHIBASHI T, MILLER JW, et al. Pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection[J]. Exp Neurol, 2009, 218(2): 347-352. doi: 10.1016/j.expneurol.2009.03.007
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (170) PDF downloads(14) Cited by()
    Proportional views
    Related

    Copyright © Journal of Nanjing University of traditional Chinese Medicine

    Sponsored by：Nanjing University of traditional Chinese MedicineAddress：No.138 xianlin Avenue, Qixia District, Nanjing cityChina Pos：210023

    Tel：025-85811935Email：xb@njucm.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return