TLR4/NF-κB/NLRP3 通路抑制炎症反应作用的研究

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Abstract Toll-like receptors (TLRs) are an important class of proteins involved in non-specific immunity,and they are one of the most important pattern recognition receptors expressed by innate immune cells.They can recognize conserved structure molecules from microorganisms,namely pathogen-associated molecular patterns (PAMAs),so as to activate the immune response.Nuclear factor kappa-B(NF-κB),which is expressed in virtually all types of cells and tissues,plays a key role in regulating the remarkable diversity of responses to external stimuli and is therefore a key factor in multiple physiological and pathological processes.NOD-like receptor protein 3(NLRP3),the NLRP3 inflammasome pathway,plays an important role in cerebral ischemia-reperfusion and pyroptosis.For example,NLRP3 is activated in microglia during cerebral ischemia-reperfusion injury and subsequently expressed in neurons and microvascular endothelial cells.The TLR/NF-κB/NLRP3 signaling pathway,which is activated by TLRs,transmitted by NF-κB and activated by NLRP3,plays a key role in the inflammatory response of various organs in the body.This paper discusses the role of various drugs in protecting major organs by inhibiting the inflammatory response of this pathway.

Key words： Toll-like receptors Nuclear factor kappa-B NOD-like receptor protein 3 Signaling pathway Inflammatory response Inhibition

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[1]	Dinarello CA，Simon A，van der Meer JW.Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases[J].Nat Rev Drug Discov，2012，11（8）：633-652.
[2]	马朋林.全身炎症反应综合征发生机制及临床干预[J].中华儿科杂志，2006（8）：599-601.
[3]	O'Neill LA，Golenbock D，Bowie AG.The history of Toll-like receptors-redefining innate immunity[J].Nat Rev Immunol，2013，13（6）：453-460.
[4]	Church JS，Kigerl KA，Lerch JK，et al.TLR4 Deficiency Impairs Oligodendrocyte Formation in the Injured Spinal Cord[J].J Neurosci，2016，36（23）：6352-6364.
[5]	Zuany-Amorim C，Hastewell J，Walker C.Toll-like receptors as potential therapeutic targets for multiple diseases[J].Nat Rev Drug Discov，2002，1（10）：797-807.
[6]	Anthoney N，Foldi I，Hidalgo A.Toll and Toll-like receptor signalling in development[J].Development，2018，145（9）：dev156018.
[7]	Hayden MS，Ghosh S.NF-κB in immunobiology[J].Cell Res，2011，21（2）：223-244.
[8]	Paerewijck O，Lamkanfi M.The human inflammasomes[J].Mol Aspects Med，2022，88：101100.
[9]	Liu J，Ma W，Zang CH，et al.Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway[J].Ann Transl Med，2021，9（22）：1694.
[10]	Bauernfeind FG，Horvath G，Stutz A，et al.Cutting edge：NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression[J].J Immunol，2009，183（2）：787-791.
[11]	杨洋，董敏，韩滨，等.溪黄草水提物对高糖诱导的大鼠HBZY-1 细胞炎症反应和氧化应激的抑制作用以及对TLR 4/NF-κB/NLRP 3 通路的作用[J].中国医院药学杂志，2019，39（21）：2157-2161.
[12]	He A，Shao J，Zhang Y，et al.CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway[J].Oncotarget，2017，8（20）：33214-33224.
[13]	Ystgaard MB，Sejersted Y，L berg EM，et al.Early Upregulation of NLRP3 in the Brain of Neonatal Mice Exposed to Hypoxia-Ischemia：No Early Neuroprotective Effects of NLRP3 Deficiency[J].Neonatology，2015，108（3）：211-219.
[14]	Colonna M，Butovsky O.Microglia Function in the Central Nervous System During Health and Neurodegeneration[J].Annu Rev Immunol，2017，35：441-468.
[15]	Liu J，Ma W，Zang CH，et al.Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway[J].Ann Transl Med，2021，9（22）：1694.
[16]	Thawkar BS，Kaur G.Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia：Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer's disease[J].J Neuroimmunol，2019，326：62-74.
[17]	黄丽萍，卢龙辉，杨喜洋，等.基于TLR4/NF-κB/NLRP3通路探讨二精丸减轻AD 大鼠神经炎症的作用及机制[J].中国中药杂志，2023，48（3）：770-777.
[18]	Mukhopadhyay S，Plüddemann A，Hoe JC，et al.Immune inhibitory ligand CD200 induction by TLRs and NLRs limits macrophage activation to protect the host from meningococcal septicemia[J].Cell Host Microbe，2010，8（3）：236-247.
[19]	Kotwica-Mojzych K，Jodlowska-Jedrych B，Mojzych M.CD200：CD200R Interactions and Their Importance in Immunoregulation[J].Int J Mol Sci，2021，22（4）：1602.
[20]	Li W，Li D，Chen Y，et al.Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS：New Research Progress and Prospect[J].Dis Markers，2022，2022：6362344.
[21]	Kim JS，Lee JY，Yang JW，et al.Immunopathogenesis and treatment of cytokine storm in COVID-19[J].Theranostics，2021，11（1）：316-329.
[22]	Ferrara JL，Abhyankar S，Gilliland DG.Cytokine storm of graft-versus-host disease：a critical effector role for interleukin-1[J].Transplant Proc，1993，25（1 Pt 2）：1216-1217.
[23]	Gan W，Li X，Cui Y，et al.Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway[J].Int Immunopharmacol，2021，90：107230.
[24]	Sen R，Baltimore D.Multiple nuclear factors interact with the immunoglobulin enhancer sequences[J].Cell，1986，46（5）：705-716.
[25]	Oeckinghaus A，Ghosh S.The NF-kappaB family of transcriptionfactorsanditsregulation[J].Cold SpringHarb Perspect Biol，2009，1（4）：a000034.
[26]	Bauernfeind FG，Horvath G，Stutz A，et al.Cutting edge：NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression[J].J Immunol，2009，183（2）：787-791.
[27]	Afonina IS，Zhong Z，Karin M，et al.Limiting inflammation-the negative regulation of NF-κB and the NLRP3 inflammasome[J].Nat Immunol，2017，18（8）：861-869.
[28]	Hausenloy DJ，Yellon DM.Myocardial ischemia-reperfusion injury：a neglected therapeutic target[J].J Clin Invest，2013，123（1）：92-100.
[29]	Ball DP，Taabazuing CY，Griswold AR，et al.Caspase-1 interdomain linker cleavage is required for pyroptosis[J].Life Sci Alliance，2020，3（3）：e202000664.
[30]	Su Q，Li L，Sun Y，et al.Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury[J].Cell Physiol Biochem，2018，47（4）：1497-1508.
[31]	IONA Study Group.Effect of nicorandil on coronary events in patients with stable angina：the Impact Of Nicorandil in Angina（IONA）randomised trial[J].Lancet，2002，359（9314）：1269-1275.
[32]	Ito H，Taniyama Y，Iwakura K，et al.Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction[J].J Am Coll Cardiol，1999，33（3）：654-660.
[33]	Ishii H，Ichimiya S，Kanashiro M，et al.Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction[J].Circulation，2005，112（9）：1284-1288.
[34]	Chen F，Chen ZQ，Zhong GL，et al.Nicorandil inhibits TLR4/MyD88/NF-κB/NLRP3 signaling pathway to reduce pyroptosis in rats with myocardial infarction[J].Exp Biol Med（Maywood），2021，246（17）：1938-1947.
[35]	Maayah ZH，Alam AS，Takahara S，et al.Resveratrol reduces cardiac NLRP3-inflammasome activation and systemic inflammation to lessen doxorubicin-induced cardiotoxicity in juvenile mice[J].FEBS Lett，2021，595（12）：1681-1695.
[36]	Hadi N，Yousif NG，Al-amran FG，et al.Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response[J].BMC Cardiovasc Disord，2012，12：63.
[37]	Zhai J，Tao L，Zhang S，et al.Calycosin ameliorates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and inflammation via the sirtuin 1-NOD-like receptor protein 3 pathway[J].Phytother Res，2020，34（3）：649-659.
[38]	Ji H，Zhang Y，Shen XD，et al.Neuropeptide PACAP in mouse liver ischemia and reperfusion injury：immunomodulation by the cAMP-PKA pathway[J].Hepatology，2013，57（3）：1225-1237.
[39]	Duffy JP，Kao K，Ko CY，et al.Long-term patient outcome and quality of life after liver transplantation：analysis of 20-year survivors[J].Ann Surg，2010，252（4）：652-661.
[40]	Guo Z，Yu S，Chen X，et al.NLRP3 Is Involved in Ischemia/Reperfusion Injury[J].CNS Neurol Disord Drug Targets，2016，15（6）：699-712.
[41]	Lu TF，Yang TH，Zhong CP，et al.Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation[J].Immune Netw，2018，18（3）：e24.
[42]	Liu Y，Lei Z，Chai H，et al.Salidroside alleviates hepatic ischemia-reperfusion injury during liver transplant in rat through regulating TLR-4/NF-κB/NLRP3 inflammatory pathway[J].Sci Rep，2022，12（1）：13973.
[43]	El-Sisi AEE，Sokar SS，Shebl AM，et al.Octreotide and melatonin alleviate inflammasome -induced pyroptosis through inhibition of TLR4-NF-κB-NLRP3 pathway in hepatic ischemia/reperfusion injury[J].Toxicol Appl Pharmacol，2021，410：115340.