| Peer-Reviewed

Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI

Received: 19 November 2021    Accepted: 6 December 2021    Published: 7 December 2021
Views:       Downloads:
Abstract

Objective: To investigate the effects of Buyang Huanwu Decoction on endoplasmic reticulum stress-autophagic response and the expression of GADD34 in ischemic penumbra of mice with CIRI. Methods: The mice were randomly divided into sham operation group, model group and Buyang Huanwu Decoction low-, medium-, and high-dosage groups. The mice were treated by gavage for 7 days before modeling and 24 hours after modeling. CIRI model was established by the thread embolization method. The neurological function was evaluated on the 48 hours after modeling; TTC staining was used to observe the cerebral infarct volume; HE staining was used to observe the pathological changes of ischemic penumbra; TUNEL was performed to assess cell apoptosis; Western blot was performed to assess the expression of endoplasmic reticulum stress marker protein GRP78 and autophagy marker proteins LC3 and p62; Immunohistochemistry and real-time PCR were applied to examine the protein and mRNA expressions of GADD34. Results: Compared with the model group, neurological function score and volume of cerebral infarction were decreased, reperfusion injury of ischemic penumbra was improved with varying degrees, number of apoptotic cells was decreased, expression of GRP78 and p62 protein were down-regulated while ratio of LC3-II/ LC3 –I was up-regulated, and expression of GADD34 protein and mRNA were up-regulated in each Buyang Huanwu Decoction group, with statistical significance (P<0.01). Conclusion Buyang Huanwu Decoction can significantly improve the damaged neurological function, cerebral infarction volume and histopathological damage of ischemic penumbra, as well as reduce the apoptosis cells, which plays a neuroprotective role in mice with CIRI. Its mechanism may be related to up regulating the expression of GADD34, regulating the steady-state balance of endoplasmic reticulum stress autophagy response in ischemic penumbra.

Published in Science Discovery (Volume 9, Issue 6)
DOI 10.11648/j.sd.20210906.33
Page(s) 417-423
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Buyang Huanwu Decoction, Cerebral Ischemia-reperfusion Injury, Endoplasmic Reticulum Stress-autophagic Response, Growth Arrest and DNA Damage-inducible Protein 34, Mice

References
[1] LAPCHAK PA. Critical early thrombolytic and endovascular reperfusion therapy for acute ischemic stroke victims: a call for adjunct neuroprotection [J]. Transl Stroke Res, 2015, 6 (5): 345-54.
[2] 李国前,王杰华,苏钦坡,等.瑞舒伐他汀对脑缺血再灌注后大鼠XIAP与Smac表达的影响[J].中国临床药理学杂志,2018,34(24):2818-2820。
[3] CHAMORRO Á, DIRNAGL U, URRA X, et al. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation [J]. Lancet Neurol, 2016, 15 (8): 869-881.
[4] 雷梦南,李玉,胡建鹏.脑缺血再灌注损伤分子生物学机制及现代中医药治疗进展[J].长春中医药大学学报,2019,35(05):991-994。
[5] 张楠,郭乐,周玉莹,等.中医药对气虚血瘀型脑缺血再灌注损伤拮抗机制的研究进展[J].长春中医药大学学报,2017,33(03):505-507。
[6] SHE Y, SHAO L, ZHANG Y, et al. Neuroprotective effect of glycosides in Buyang Huanwu Decoction on pyroptosis following cerebral ischemia-reperfusion injury in rats [J]. J Ethnopharmacol, 2019, 242: 112051.
[7] JIANG C, XU YC, ZHANG W, et al. Effects and safety of Buyang-Huanwu Decoction for the treatment of patients with acute ischemic stroke: A protocol of systematic review and meta-analysis [J]. Medicine (Baltimore), 2020, 99 (23): e20534.
[8] AHSAN A, ZHENG YR, WU XL, et al. Urolithin A-activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo [J]. CNS Neurosci Ther, 2019, 25 (9): 976-986.
[9] YIN Y, SUN G, LI E, et al. ER stress and impaired autophagy flux in neuronal degeneration and brain injury [J]. Ageing Res Rev, 2017, 34: 3-14.
[10] HOLCZER M, BESZE B, ZáMBó V, et al. Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress [J]. Oxid Med Cell Longev, 2018, 2018: 6721530.
[11] 贺石林,王键,王净净.中医科研设计与统计学[M].湖南:科学技术出版社,2012.48-49。
[12] 周胜强,易健,周赛男,等.补阳还五汤对局灶性脑缺血小鼠半暗带细胞自噬水平的影响[J].湖南中医杂志,2017,33(02):119-123。
[13] LONGA EZ, WEINSTEIN PR, CARLSON S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke, 1989, 20 (1): 84-91.
[14] CLARK WM, LESSOV NS, DIXON MP, et al. Monofilament intraluminal middle cerebral artery occlusion in the mouse [J]. Neurol Res, 1997, 19 (6): 641-8.
[15] 张颖,陈自雅,刘强,等.补阳还五汤对脑缺血再灌注大鼠脑损伤的保护作用[J].中华老年心脑血管病杂志,2019,21(08):867-870。
[16] KAPUY O, MáRTON M, BáNHEGYI G, et al. Multiple system-level feedback loops control life-and-death decisions in endoplasmic reticulum stress [J]. FEBS Lett, 2020, 594 (6): 1112-1123.
[17] CHU Q, MARTINEZ TF, NOVAK SW, et al. Regulation of the ER stress response by a mitochondrial microprotein [J]. Nat Commun, 2019, 10 (1): 4883.
[18] HOLCZER M, MáRTON M, KURUCZ A, et al. A Comprehensive Systems Biological Study of Autophagy-Apoptosis Crosstalk during Endoplasmic Reticulum Stress[J]. Biomed Res Int, 2015, 2015: 319589.
[19] CAI Y, ARIKKATH J, YANG L, et al. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders [J]. Autophagy, 2016, 12 (2): 225-44.
[20] QI Z, CHEN L. Endoplasmic Reticulum Stress and Autophagy[J]. Adv Exp Med Biol, 2019, 1206: 167-177.
[21] 申向民,杨期东,谭利明,等.大鼠脑缺血再灌注后梗死周边区GADD34的表达变化[J].中国神经精神疾病杂志,2010,36(11):676-678。
[22] NAKKA VP, PRAKASH-BABU P, VEMUGANTI R. Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries [J]. Mol Neurobiol, 2016, 53 (1): 532-544.
Cite This Article
  • APA Style

    Zhou Shengqiang, Li Bo, Liu Fang. (2021). Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI. Science Discovery, 9(6), 417-423. https://doi.org/10.11648/j.sd.20210906.33

    Copy | Download

    ACS Style

    Zhou Shengqiang; Li Bo; Liu Fang. Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI. Sci. Discov. 2021, 9(6), 417-423. doi: 10.11648/j.sd.20210906.33

    Copy | Download

    AMA Style

    Zhou Shengqiang, Li Bo, Liu Fang. Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI. Sci Discov. 2021;9(6):417-423. doi: 10.11648/j.sd.20210906.33

    Copy | Download

  • @article{10.11648/j.sd.20210906.33,
      author = {Zhou Shengqiang and Li Bo and Liu Fang},
      title = {Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI},
      journal = {Science Discovery},
      volume = {9},
      number = {6},
      pages = {417-423},
      doi = {10.11648/j.sd.20210906.33},
      url = {https://doi.org/10.11648/j.sd.20210906.33},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sd.20210906.33},
      abstract = {Objective: To investigate the effects of Buyang Huanwu Decoction on endoplasmic reticulum stress-autophagic response and the expression of GADD34 in ischemic penumbra of mice with CIRI. Methods: The mice were randomly divided into sham operation group, model group and Buyang Huanwu Decoction low-, medium-, and high-dosage groups. The mice were treated by gavage for 7 days before modeling and 24 hours after modeling. CIRI model was established by the thread embolization method. The neurological function was evaluated on the 48 hours after modeling; TTC staining was used to observe the cerebral infarct volume; HE staining was used to observe the pathological changes of ischemic penumbra; TUNEL was performed to assess cell apoptosis; Western blot was performed to assess the expression of endoplasmic reticulum stress marker protein GRP78 and autophagy marker proteins LC3 and p62; Immunohistochemistry and real-time PCR were applied to examine the protein and mRNA expressions of GADD34. Results: Compared with the model group, neurological function score and volume of cerebral infarction were decreased, reperfusion injury of ischemic penumbra was improved with varying degrees, number of apoptotic cells was decreased, expression of GRP78 and p62 protein were down-regulated while ratio of LC3-II/ LC3 –I was up-regulated, and expression of GADD34 protein and mRNA were up-regulated in each Buyang Huanwu Decoction group, with statistical significance (PConclusion Buyang Huanwu Decoction can significantly improve the damaged neurological function, cerebral infarction volume and histopathological damage of ischemic penumbra, as well as reduce the apoptosis cells, which plays a neuroprotective role in mice with CIRI. Its mechanism may be related to up regulating the expression of GADD34, regulating the steady-state balance of endoplasmic reticulum stress autophagy response in ischemic penumbra.},
     year = {2021}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Effects of Buyang Huanwu Decoction on Endoplasmic Reticulum Stress-Autophagy Response and GADD34 Expression in Mice with CIRI
    AU  - Zhou Shengqiang
    AU  - Li Bo
    AU  - Liu Fang
    Y1  - 2021/12/07
    PY  - 2021
    N1  - https://doi.org/10.11648/j.sd.20210906.33
    DO  - 10.11648/j.sd.20210906.33
    T2  - Science Discovery
    JF  - Science Discovery
    JO  - Science Discovery
    SP  - 417
    EP  - 423
    PB  - Science Publishing Group
    SN  - 2331-0650
    UR  - https://doi.org/10.11648/j.sd.20210906.33
    AB  - Objective: To investigate the effects of Buyang Huanwu Decoction on endoplasmic reticulum stress-autophagic response and the expression of GADD34 in ischemic penumbra of mice with CIRI. Methods: The mice were randomly divided into sham operation group, model group and Buyang Huanwu Decoction low-, medium-, and high-dosage groups. The mice were treated by gavage for 7 days before modeling and 24 hours after modeling. CIRI model was established by the thread embolization method. The neurological function was evaluated on the 48 hours after modeling; TTC staining was used to observe the cerebral infarct volume; HE staining was used to observe the pathological changes of ischemic penumbra; TUNEL was performed to assess cell apoptosis; Western blot was performed to assess the expression of endoplasmic reticulum stress marker protein GRP78 and autophagy marker proteins LC3 and p62; Immunohistochemistry and real-time PCR were applied to examine the protein and mRNA expressions of GADD34. Results: Compared with the model group, neurological function score and volume of cerebral infarction were decreased, reperfusion injury of ischemic penumbra was improved with varying degrees, number of apoptotic cells was decreased, expression of GRP78 and p62 protein were down-regulated while ratio of LC3-II/ LC3 –I was up-regulated, and expression of GADD34 protein and mRNA were up-regulated in each Buyang Huanwu Decoction group, with statistical significance (PConclusion Buyang Huanwu Decoction can significantly improve the damaged neurological function, cerebral infarction volume and histopathological damage of ischemic penumbra, as well as reduce the apoptosis cells, which plays a neuroprotective role in mice with CIRI. Its mechanism may be related to up regulating the expression of GADD34, regulating the steady-state balance of endoplasmic reticulum stress autophagy response in ischemic penumbra.
    VL  - 9
    IS  - 6
    ER  - 

    Copy | Download

Author Information
  • Affiliated Hospital, Hunan Academy of Chinese Medicine, Changsha, China

  • The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, China

  • Affiliated Hospital, Hunan Academy of Chinese Medicine, Changsha, China

  • Sections