Mechanism of CGAS-STING Signaling Pathway in Regulating Ischemic Stroke and Intervention of Traditional Chinese Medicine： A Review

LI Jiazheng; XU Junfeng

doi:10.13422/j.cnki.syfjx.20241997

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Mechanism of CGAS-STING Signaling Pathway in Regulating Ischemic Stroke and Intervention of Traditional Chinese Medicine： A Review

更新时间：2024-07-31

- Mechanism of CGAS-STING Signaling Pathway in Regulating Ischemic Stroke and Intervention of Traditional Chinese Medicine： A Review
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 17, Pages: 284-291(2024)
- 作者机构：
  
  1.天津中医药大学第一附属医院，国家中医针灸临床医学研究中心，天津 301617
  2.天津中医药大学，天津 301617
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20241997
  CLC： R242;R2-0;R2-031;R259;R287;R255.2;R743.3
- Published：05 September 2024，
  
  Published Online：20 June 2024，
  
  Received：29 January 2024，
- 稿件说明：
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李家正,许军峰.cGAS/STING信号通路调控缺血性脑卒中的机制及中药干预研究进展[J].中国实验方剂学杂志,2024,30(17):284-291.

LI Jiazheng,XU Junfeng.Mechanism of CGAS-STING Signaling Pathway in Regulating Ischemic Stroke and Intervention of Traditional Chinese Medicine： A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(17):284-291.
李家正,许军峰.cGAS/STING信号通路调控缺血性脑卒中的机制及中药干预研究进展[J].中国实验方剂学杂志,2024,30(17):284-291. DOI： 10.13422/j.cnki.syfjx.20241997.

LI Jiazheng,XU Junfeng.Mechanism of CGAS-STING Signaling Pathway in Regulating Ischemic Stroke and Intervention of Traditional Chinese Medicine： A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(17):284-291. DOI： 10.13422/j.cnki.syfjx.20241997.

摘要

缺血性脑卒中是临床常见的脑血管疾病，其发病率逐年上升。针对卒中的临床治疗目前以溶栓及静脉取栓等为主，这两种方式受时间限制较大，遗留病症较多，降低患者生存质量。研究发现，在卒中病理过程中存在多种通路机制，其中环鸟苷酸-腺苷酸合成酶（cGAS）/干扰素基因刺激因子（STING）通路就是其中一种。目前针对缺血性脑卒中的发生发展及中药干预卒中的机制国内外研究人员做了大量研究，结果发现中药调控cGAS/STING通路可以降低炎症反应和氧化应激，并减少神经细胞死亡，有效减轻卒中的脑损伤，对于改善卒中的症状及改善预后方面具有独特优势。该文主要归纳总结了近年来cGAS/STING通路调控卒中的机制及相关中药干预研究进展，以期为缺血性脑卒中的中医药特色治疗提供新思路。

Abstract

Ischemic stroke is a common clinical cerebrovascular disease，and its incidence is increasing year by year. Current clinical treatments for stroke mainly include thrombolysis and intravenous thrombectomy，both of which are subject to significant time constraints and often result in residual symptoms，reducing the quality of life for patients. Research has found that there are multiple pathways and mechanisms in the pathological process of stroke，such as the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon gene （STING） pathway. Currently，researchers in China and abroad have conducted extensive studies on the occurrence and development of ischemic stroke， as well as the mechanism of traditional Chinese medicine （TCM） intervention for stroke. The results indicate that traditional Chinese medicine（TCM） can regulate the cGAS/STING pathway to reduce inflammation and oxidative stress，decrease neuronal cell death，and effectively alleviate brain damage from stroke，and it has unique advantages in improving symptoms and prognosis. This article summarized the recent research progress of the mechanism of cGAS/STING pathway regulation in stroke and related TCM intervention，so as to provide new ideas for the treatment of ischemic stroke with TCM characteristics.

关键词

缺血性脑卒中环鸟苷酸-腺苷酸合成酶（cGAS）干扰素基因刺激因子中医药作用机制

Keywords

ischemic strokecyclic GMP-AMP synthase（cGAS）stimulator of interferon genetraditional Chinese medicinemechanism of action

references

FAN J，LI X，YU X，et al.Global burden，risk factor analysis，and prediction study of ischemic stroke，1990-2030［J］.Neurology，2023，101（2）：e137-e150.

KRANZUSCH P J，LEE A S，BERGER J M，et al.Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity［J］.Cell Rep，2013，3（5）：1362-1368.

MA X，XIN D，SHE R，et al.Novel insight into cGAS-STING pathway in ischemic stroke：From pre- to post-disease［J］.Front Immunol，2023，14：1275408.

CHAUHAN C，KAUNDAL R K.The role of cGAS-STING signaling in ischemic stroke：From immune response to therapeutic targeting［J］.Drug Discov Today，2023，28（11）：103792.

HOPFNER K P，HORNUNG V.Molecular mechanisms and cellular functions of cGAS-STING signalling［J］.Nat Rev Mol Cell Biol，2020，21（9）：501-521.

GONZALO S，COLL-BONFILL N.Genomic instability and innate immune responses to self-DNA in progeria［J］.Geroscience，2019，41（3）：255-266.

李文欣，张贺峰，谢作权，等.cGAS-STING通路异常激活及其抑制剂在免疫和炎症疾病中的研究进展［J］.中国药理学通报，2023，39（11）：2001-2005.

CHEN X，WANG L，CAO L，et al.Regulation of anion channel LRRC8 volume-regulated anion channels in transport of 2'3'-Cyclic GMP-AMP and cisplatin under steady state and inflammation［J］.J Immunol，2021，206（9）：2061-2074.

GULEN M F，SAMSON N，KELLER A，et al.cGAS-STING drives ageing-related inflammation and neurodegeneration［J］.Nature，2023，620（7973）：374-380.

SHI K，TIAN D C，LI Z G，et al.Global brain inflammation in stroke［J］.Lancet Neurol，2019，18（11）：1058-1066.

LIAO Y，CHENG J，KONG X，et al.HDAC3 inhibition ameliorates ischemia/reperfusion-induced brain injury by regulating the microglial cGAS-STING pathway［J］.Theranostics，2020，10（21）：9644-9662.

ZHU Z，LU H，JIN L，et al.C-176 loaded Ce DNase nanoparticles synergistically inhibit the cGAS-STING pathway for ischemic stroke treatment［J］.Bioact Mater，2023，29：230-240.

JIANG G L，YANG X L，ZHOU H J，et al.cGAS knockdown promotes microglial M2 polarization to alleviate neuroinflammation by inhibiting cGAS-STING signaling pathway in cerebral ischemic stroke［J］.Brain Res Bull，2021，171：183-195.

DING R，LI H，LIU Y，et al.Activating cGAS-STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis［J］.J Neuroinflammation，2022，19（1）：137.

LI Q，CAO Y，DANG C，et al.Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke［J］.EMBO Mol Med，2020，12（4）：e11002.

KONG L，LI W，CHANG E，et al.mtDNA-STING axis mediates microglial polarization via IRF3/NF-κB signaling after ischemic stroke［J］.Front Immunol，2022，13：860977.

SUN S，LV W，LI S，et al.Smart liposomal nanocarrier enhanced the treatment of ischemic stroke through neutrophil extracellular traps and cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes （cGAS-STING） pathway inhibition of ischemic penumbra［J］.ACS Nano，2023，17（18）：17845-17857.

WANG R，ZHU Y，LIU Z，et al.Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke［J］.Blood，2021，138（1）：91-103.

KANG L，YU H，YANG X，et al.Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke［J］.Nat Commun，2020，11（1）：2488.

ZHAO J，ZHEN N，ZHOU Q，et al.NETs promote inflammatory injury by activating cGAS-STING pathway in acute lung injury［J］.Int J Mol Sci，2023，24（6）：5125.

LI B，WANG W，LI Y，et al.cGAS-STING pathway aggravates early cerebral ischemia-reperfusion injury in mice by activating NCOA4-mediated ferritinophagy［J］.Exp Neurol，2023，359：114269.

ANDRADE B，JARA-GUTIÉRREZ C，PAZ-ARAOS M，et al.The Relationship between reactive oxygen species and the cGAS/STING signaling pathway in the inflammaging process［J］.Int J Mol Sci，2022，23（23）：15182.

TAO L，LEMOFF A，WANG G，et al.Reactive oxygen species oxidize STING and suppress interferon production［J］.Elife，2020，9：e57837.

CHEN Y，FANG Z M，YI X，et al.The interaction between ferroptosis and inflammatory signaling pathways［J］.Cell Death Dis，2023，14（3）：205.

JIA M，QIN D，ZHAO C，et al.Redox homeostasis maintained by GPX4 facilitates STING activation［J］.Nat Immunol，2020，21（7）：727-735.

TANG D，CHEN X，KANG R，et al.Ferroptosis：molecular mechanisms and health implications［J］.Cell Res，2021，31（2）：107-125.

VILA I K，CHAMMA H，STEER A，et al.STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses［J］.Cell Metab，2022，34（1）：125-139.e8.

YUAN B，ZHOU X M，YOU Z Q，et al.Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage［J］.Cell Death Dis，2020，11（1）：76.

CHENG Q，PAN J，ZHOU Z L，et al.Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy［J］.Acta Pharmacol Sin，2021，42（6）：954-963.

LIU J，ZHOU J，LUAN Y，et al.cGAS-STING，inflammasomes and pyroptosis：An overview of crosstalk mechanism of activation and regulation［J］.Cell Commun Signal，2024，22（1）：22.

AARREBERG L D，ESSER-NOBIS K，DRISCOLL C，et al.Interleukin-1β induces mtDNA release to activate innate immune signaling via cGAS-STING［J］.Mol Cell，2019，74（4）：801-815.

TANG D，KANG R，BERGHE T V，et al.The molecular machinery of regulated cell death［J］.Cell Res，2019，29（5）：347-364.

MCARTHUR K，WHITEHEAD L W，HEDDLESTON J M，et al.Bak/Bax macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis［J］.Science，2018，359（6378）：eaao6047.

SINGH R，LETAI A，SAROSIEK K.Regulation of apoptosis in health and disease：The balancing act of BCL-2 family proteins［J］.Nat Rev Mol Cell Biol，2019，20（3）：175-193.

XU Y，CHEN C，LIAO Z，et al.cGAS-STING signaling in cell death：Mechanisms of action and implications in pathologies［J］.Eur J Immunol，2023，53（9）：e2350386.

LIAO S，APAIJAI N，CHATTIPAKORN N，et al.The possible roles of necroptosis during cerebral ischemia and ischemia/reperfusion injury［J］.Arch Biochem Biophys，2020，695：108629.

FANN D Y，LEE S Y，MANZANERO S，et al.Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke［J］.Cell Death Dis，2013，4（9）：e790.

WANG L，CHANG X，FENG J，et al.TRADD mediates RIPK1-independent necroptosis induced by tumor necrosis factor［J］.Front Cell Dev Biol，2019，7：393.

BRAULT M，OLSEN T M，MARTINEZ J，et al.Intracellular nucleic acid sensing triggers necroptosis through synergistic type Ⅰ IFN and TNF signaling［J］.J Immunol，2018，200（8）：2748-2756.

SCHNEIDER W M，CHEVILLOTTE M D，RICE C M.Interferon-stimulated genes：A complex web of host defenses［J］.Annu Rev Immunol，2014，32：513-545.

WARRE-CORNISH K，PERFECT L，NAGY R，et al.Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes［J］.Sci Adv，2020，6（34）：eaay9506.

YASUDA M，NAGAPPAN-CHETTIAR S，JOHNSON-VENKATESH E M，et al.An activity-dependent determinant of synapse elimination in the mammalian brain［J］.Neuron，2021，109（8）：1333-1349.

WANG X，YANG C，WANG X，et al.Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFNγ-cGAS-STING axis［J］.Neuron，2023，111（2）：236-255.

BECK H，PLATE K H.Angiogenesis after cerebral ischemia［J］.Acta Neuropathol，2009，117（5）：481-496.

LUO J，LU C，CHEN Y，et al.Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis［J］.Cell Rep，2023，42（4）：112328.

CHEN Q，TANG L，ZHANG Y，et al.STING up-regulates VEGF expression in oxidative stress-induced senescence of retinal pigment epithelium via NF-κB/HIF-1α pathway［J］.Life Sci，2022，293：120089.

LI S，HONG Z，WANG Z，et al.The cyclopeptide astin C specifically inhibits the innate immune CDN sensor STING［J］.Cell Rep，2018，25（12）：3405-3421.

周云，屠思维，傅美香.决明子水提物对脑缺血/再灌注损伤大鼠的脑保护作用及对cGAS/STING通路的影响［J］.中国药师，2021，24（10）：1823-1828.

吴艺帆，傅晨，罗超琴，等.三七总皂苷调控cGAS/STING/NF-κB通路对急性脑梗死大鼠炎症反应的影响［J］.北京中医药，2021，40（10）：1061-1065.

段兆达，徐冬垚，杨毓甲，等.灯盏乙素对大鼠脑缺血后小胶质细胞cGAS/STING/NLRP3信号轴的调控［J］.神经解剖学杂志，2023，39（5）：517-522.

XUE W，LI Y，ZHANG M.Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling［J］.Pharm Biol，2021，59（1）：1351-1358.

林晓燕，方丽鑫，黄丽霞，等.扁蒴藤素调节cGAS/STING信号通路对缺血性脑卒中大鼠认知功能和神经炎症的影响［J］.河北医学，2023，29（11）：1761-1767.

CHEN Y Y，LIU Q P，AN P，et al.Ginsenoside Rd：A promising natural neuroprotective agent［J］.Phytomedicine，2022，95：153883.

LI Y，YU P，FU W，et al.Ginsenoside Rd inhibited ferroptosis to alleviate CCl4-induced acute liver injury in mice via cGAS/STING pathway［J］.Am J Chin Med，2023，51（1）：91-105.

LU J，ZHANG Y，DONG H，et al.New mechanism of nephrotoxicity of triptolide：Oxidative stress promotes cGAS-STING signaling pathway［J］.Free Radic Biol Med，2022，188：26-34.

姬彦兆，项磊，杨乐斌，等.罗仁诊治肾病学术思想与临床经验介绍［J］.新中医，2017，49（3）：180-182.

QI J，LUO Q，ZHANG Q，et al.Yi-Shen-Xie-Zhuo formula alleviates cisplatin-induced AKI by regulating inflammation and apoptosis via the cGAS/STING pathway［J］.J Ethnopharmacol，2023，309：116327.

SHI W，XU G，GAO Y，et al.Compound Danshen Dripping pill effectively alleviates cGAS-STING-triggered diseases by disrupting STING-TBK1 interaction［J］.Phytomedicine，2024，128：155404.

WANG J，HU J，LIU Y，et al.Dominant cardiovascular diseases treated by traditional Chinese medicine：clinical evidence and distinctive therapeutic char_x0002_acteristics［J］.Sci Tradit Chin Med 2023，1（1）：19-25.

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