浏览全部资源
扫码关注微信
1.甘肃中医药大学,兰州 730000
2.甘肃省中医院,兰州 730000
Published:20 November 2023,
Published Online:13 February 2023,
Received:19 November 2022,
扫 描 看 全 文
张团庄,宋渊,何志军等.中药干预NLRP3炎症小体治疗骨关节相关疾病研究进展[J].中国实验方剂学杂志,2023,29(22):193-203.
ZHANG Tuanzhuang,SONG Yuan,HE Zhijun,et al.Chinese Medicine Intervenes in NLRP3 Inflammasome in Treatment of Bone and Joint Diseases: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(22):193-203.
张团庄,宋渊,何志军等.中药干预NLRP3炎症小体治疗骨关节相关疾病研究进展[J].中国实验方剂学杂志,2023,29(22):193-203. DOI: 10.13422/j.cnki.syfjx.20230508.
ZHANG Tuanzhuang,SONG Yuan,HE Zhijun,et al.Chinese Medicine Intervenes in NLRP3 Inflammasome in Treatment of Bone and Joint Diseases: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(22):193-203. DOI: 10.13422/j.cnki.syfjx.20230508.
骨关节疾病患病率正随着我国社会老年人口数量的不断增加正在逐年攀升,常见的骨关节疾病包括骨质疏松、骨性关节炎、痛风性关节炎、类风湿性关节炎、椎间盘退变,其临床表现主要共同点就是不同部位的剧烈疼痛,严重影响患者日常生活。故而如何缓解骨关节疾病疼痛,降低骨关节疾病患病率,提高患者生活质量,是当今医学领域研究的重要课题和热点。研究证实,NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体作为一种模式识别受体,通过参与骨关节疾病炎症反应、软骨细胞增殖、成骨细胞和破骨细胞的分化、椎间盘细胞的炎症与焦亡、细胞外基质降解和凋亡、线粒体功能障碍、内质网应激及活性氧损伤,与骨关节相关疾病的发生发展有着紧密的联系。中医药治疗骨关节相关疾病历史悠久,疗效显著,且占据着重要的治疗地位。同时有研究表明,中医药能够通过抑制NLRP3炎症小体,改善骨关节疾病病理改变,缓解骨关节疾病带来的疼痛,发挥防治骨关节疾病的作用。因此,该文通过查阅了国内外最新研究进展,简单阐述了NLRP3炎症小体与骨关节疾病发生发展的关系,并总结了中药单体、中药提取物及中药复方干预NLRP3炎症小体治疗骨关节疾病的最新研究报道,以期为骨关节疾病发病机制及药物治疗的深入研究提供新思路,为临床上运用中医药防治骨关节疾病提供依据。
The prevalence of osteoporosis, osteoarthritis, gouty arthritis, rheumatoid arthritis, and intervertebral disc degeneration is increasing year by year with the growing number of elderly people, and the common clinical manifestations of these diseases include severe pain in different areas, which seriously affects the daily life of the patients. Therefore, how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasomes, as pattern recognition receptors, are involved in the inflammation, chondrocyte proliferation, osteoblast and osteoclast differentiation, intervertebral disc cell inflammation and scorching, extracellular matrix degradation and apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and reactive oxygen species damage, demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain, playing a role in preventing and treating these diseases. Therefore, this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components, extracts, and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.
NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体中医药骨质疏松骨性关节炎痛风性关节炎类风湿性关节炎椎间盘退变
NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasomeChinese medicineosteoporosisosteoarthritisgouty arthritisrheumatoid arthritisintervertebral disc degeneration
HUNTER D J,BIERMA-ZEINSTRA S.Osteoarthritis[J].Lancet,2019,393(10182):1745-1759.
SAFIRI S,KOLAHI A A,SMITH E,et al.Global,regional and national burden of osteoarthritis 1990-2017:A systematic analysis of the Global Burden of Disease Study 2017[J].Ann Rheum Dis,2020,79(6):819-828.
YU C,ZHANG C,KUANG Z,et al.The role of NLRP3 inflammasome activities in bone diseases and vascular calcification[J].Inflammation,2021,44(2):434-449.
TSENG H W,SAMUEL S G,SCHRODER K,et al.Inflammasomes and the IL-1 family in bone homeostasis and disease[J].Curr Osteoporos Rep,2022,20(3):170-185.
CLAUZURE M,VALDIVIESO Á G,DUGOUR A V,et al.NLR family pyrin domain containing 3 (NLRP3) and Caspase 1 (CASP1) modulation by intracellular Cl- concentration[J].Immunology,2021,163(4):493-511.
KELLEY N,JELTEMA D,DUAN Y,et al.The NLRP3 inflammasome:An overview of mechanisms of activation and regulation[J].Int J Mol Sci,2019,20(13):3328-3328.
HUANG Y,XU W,ZHOU R.NLRP3 inflammasome activation and cell death[J].Cell Mol Immunol,2021,18(9):2114-2127.
WANG W,PANG J,HA E H,et al.Development of novel NLRP3-XOD dual inhibitors for the treatment of gout[J].Bioorg Med Chem Lett,2020,30(4):126944.
GUO C,FU R,WANG S,et al.NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis[J].Clin Exp Immunol,2018,194(2):231-243.
CHAO-YANG G,PENG C,HAI-HONG Z.Roles of NLRP3 inflammasome in intervertebral disc degeneration[J].Osteoarthritis Cartilage,2021,29(6):793-801.
ROŠKAR S,HAFNER-BRATKOVIČ I.The role of inflammasomes in osteoarthritis and secondary joint degeneration diseases[J].Life (Basel),2022,12(5):731-731.
MURAKAMI T,NAKAMINAMI Y,TAKAHATA Y,et al.Activation and function of NLRP3 inflammasome in bone and joint-related diseases[J].Int J Mol Sci,2022,23(10):5365-5365.
李辉,谢兴文,李宁,等.肠道菌群与骨关节疾病的关系及中医药调节研究进展[J].中国实验方剂学杂志,2022,28(7):268-275.
唐秀松,赵心怡,陈静,等.基于细胞焦亡理论探讨中医药防治类风湿关节炎研究进展[J].中国实验方剂学杂志,2022,28(19):231-240.
魏晓涛,何志军,刘涛,等.中药干预皮瓣血管再生相关信号通路研究进展[J].中国实验方剂学杂志,2023,29(19):275-282.
COMPSTON J E,MCCLUNG M R,LESLIE W D.Osteoporosis[J].Lancet,2019,393(10169):364-376.
CLINE-SMITH A,AXELBAUM A,SHASHKOVA E,et al.Ovariectomy activates chronic low-grade inflammation mediated by memory T cells,which promotes osteoporosis in mice[J].J Bone Miner Res,2020,35(6):1174-1187.
ALIPPE Y,WANG C,RICCI B,et al.Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation[J].Sci Rep,2017,7(1):6630-6630.
DETZEN L,CHEAT B,BESBES A,et al.NLRP3 is involved in long bone edification and the maturation of osteogenic cells[J].J Cell Physiol,2021,236(6):4455-4469.
ROCHA F R G,DELITTO A E,DE SOUZA J A C,et al.Relevance of Caspase-1 and Nlrp3 inflammasome on inflammatory bone resorption in a murine model of periodontitis[J].Sci Rep,2020,10(1):7823-7823.
WANG C,XIAO J,NOWAK K,et al.PARP1 hinders histone H2B occupancy at the NFATc1 promoter to restrain osteoclast differentiation[J].J Bone Miner Res,2020,35(4):776-788.
MANSOORI M N,SHUKLA P,KAKAJI M,et al.IL-18BP is decreased in osteoporotic women:Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation[J].Sci Rep,2016,6:33680.
XU L,ZHANG L,WANG Z,et al.Melatonin suppresses estrogen deficiency-induced osteoporosis and promotes osteoblastogenesis by inactivating the NLRP3 inflammasome[J].Calcif Tissue Int,2018,103(4):400-410.
SARTORETTO S,GEMINI-PIPERNI S,DA SILVA R A ,et al.Apoptosis-associated speck-like protein containing a Caspase-1 recruitment domain (ASC) contributes to osteoblast differentiation and osteogenesis[J].J Cell Physiol,2019,234(4):4140-4153.
JIANG N,AN J,YANG K,et al.NLRP3 inflammasome:A new target for prevention and control of osteoporosis?[J].Front Endocrinol (Lausanne),2021,12:752546-752546.
QUICKE J G,CONAGHAN P G,CORP N,et al.Osteoarthritis year in review 2021:Epidemiology & therapy[J].Osteoarthritis Cartilage,2022,30(2):196-206.
MCALLISTER M J,CHEMALY M,EAKIN A J,et al.NLRP3 as a potentially novel biomarker for the management of osteoarthritis[J].Osteoarthritis Cartilage,2018,26(5):612-619.
BAI H,ZHANG Z,LIU L,et al.Activation of adenosine A3 receptor attenuates progression of osteoarthritis through inhibiting the NLRP3/Caspase-1/GSDMD induced signalling[J].J Cell Mol Med,2022,26(15):4230-4243.
CHEN Z,ZHONG H,WEI J,et al.Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis[J].Arthritis Res Ther,2019,21(1):300.
LUO Y,XIONG B,LIU H,et al.Koumine suppresses IL-1β secretion and attenuates inflammation associated with blocking ROS/NF-κB/NLRP3 axis in macrophages[J].Front Pharmacol,2020,11:622074.
LIU J,HUANG X,ZHOU J,et al.Pulsed electromagnetic field alleviates synovitis and inhibits the NLRP3/Caspase-1/GSDMD signaling pathway in osteoarthritis rats[J].Electromagn Biol Med,2022,41(1):101-107.
ZHANG L,QIU J,SHI J,et al.MicroRNA-140-5p represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3[J].Bioengineered,2021,12(2):9949-9964.
ZHUANG Y,WANG H,SU J,et al.A narrative review of positive regulation of NLRP3 inflammasome in rheumatoid arthritis[J].Ann Palliat Med,2021,10(12):12877-12885.
NASROLLAHZADEH SABET M,NASRABADI N,JALILI Z,et al.Association of three functional polymorphisms in the NLRP3 gene with susceptibility to rheumatoid arthritis in the iranian population[J].Iran J Immunol,2021,18(3):249-258.
CHENG L,LIANG X,QIAN L,et al.NLRP3 gene polymorphisms and expression in rheumatoid arthritis[J].Exp Ther Med,2021,22(4):1110-1110.
CHOULAKI C,PAPADAKI G,REPA A,et al.Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis[J].Arthritis Res Ther,2015,17(1):257.
WANG Z,KUN Y,LEI Z,et al.LncRNA MIAT downregulates IL-1β,TNF-α to suppress macrophage inflammation but is suppressed by ATP-induced NLRP3 inflammasome activation[J].Cell Cycle,2021,20(2):194-203.
COLL R C,SCHRODER K,PELEGRÍN P.NLRP3 and pyroptosis blockers for treating inflammatory diseases[J].Trends Pharmacol Sci,2022,43(8):653-668.
CUTOLO M,CAMPITIELLO R,GOTELLI E,et al.The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis[J].Front Immunol,2022,13:867260.
VIDAL F,GILLIBERT A,QUILLARD M,et al.Does iron deficiency contribute to fatigue in patients with rheumatoid arthritis without anemia?[J].Joint Bone Spine,2020,87(1):89.
DEHLIN M,JACOBSSON L,RODDY E.Global epidemiology of gout:Prevalence,incidence,treatment patterns and risk factors[J].Nat Rev Rheumatol,2020,16(7):380-390.
MANGAN M S J,OLHAVA E J,ROUSH W R,et al.Targeting the NLRP3 inflammasome in inflammatory diseases[J].Nat Rev Drug Discov,2018,17(9):688.
ZHANG Q B,QING Y F,HE Y L,et al.Association of NLRP3 polymorphisms with susceptibility to primary gouty arthritis in a Chinese Han population[J].Clin Rheumatol,2018,37(1):235-244.
RENAUDIN F,ORLIAGUET L,CASTELLI F,et al.Gout and pseudo-gout-related crystals promote GLUT1-mediated glycolysis that governs NLRP3 and interleukin-1β activation on macrophages[J].Ann Rheum Dis,2020,79(11):1506-1514.
LI X,LIU Y,LUO C,et al.Z1456467176 alleviates gouty arthritis by allosterically modulating P2X7R to inhibit NLRP3 inflammasome activation[J].Front Pharmacol,2022,13:979939.
WU C,CHEN S,LIU Y,et al.Cynarin suppresses gouty arthritis induced by monosodium urate crystals[J].Bioengineered,2022,13(5):11782-11793.
ATLURI S,MURPHY M B,DRAGELLA R,et al.Evaluation of the effectiveness of autologous bone marrow mesenchymal stem cells in the treatment of chronic low back pain due to severe lumbar spinal degeneration:A 12-month,open-label,prospective controlled trial[J].Pain Physician,2022,25(2):193-207.
XIN J,WANG Y,ZHENG Z,et al.Treatment of intervertebral disc degeneration[J].Orthop Surg,2022,14(7):1271-1280.
BAI Z,LIU W,HE D,et al.Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells[J].Aging (Albany NY),2020,12(8):7534-7548.
CHEN F,JIANG G,LIU H,et al.Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop[J].Bone Res,2020,8:10.
CHEN S,WU X,LAI Y,et al.Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc[J].Bone Res,2022,10(1):5.
YUAN X,LI T,SHI L,et al.Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3[J].Mol Med,2021,27(1):91.
左远胜,何智圣,付中明,等.防己诺林碱通过Nrf2/NLRP3途径对去卵巢骨质疏松大鼠骨结构和成骨细胞凋亡的影响[J].实用药物与临床,2021,24(10):881-886.
XU L,SHEN L,YU X,et al.Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome[J].Exp Ther Med,2020,19(2):1084-1090.
LI Q,TAO X,ZHANG Y.Rosmarinic acid alleviates diabetic osteoporosis by suppressing the activation of NLRP3 inflammasome in rats[J].Physiol Int,2022,doi:10.1556/2060.2022.00154http://dx.doi.org/10.1556/2060.2022.00154.
LU L,WANG Z,ZHANG H,et al.Drynaria fortunei improves lipid profiles of elderly patients with postmenopausal osteoporosis via regulation of Notch1-NLRP3 inflammasome-mediated inflammation[J].Gynecol Endocrinol,2022,38(2):176-180.
YI N,MI Y,XU X,et al.Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1/ROS/NLRP3 axis[J].Int Immunopharmacol,2022,113(Pt A):109349.
ZHANG L,LI X,ZHANG H,et al.Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through the inhibition of HIF-1α and NLRP3 inflammasome[J].Mediators Inflamm,2021,2021:5534614.
LI W,WANG Y,TANG Y,et al.Quercetin alleviates osteoarthritis progression in rats by suppressing inflammation and apoptosis via inhibition of IRAK1/NLRP3 signaling[J].J Inflamm Res,2021,14:3393-3403.
WANG Q,YING L,WEI B,et al.Effects of quercetin on apoptosis and extracellular matrix degradation of chondrocytes induced by oxidative stress-mediated pyroptosis[J].J Biochem Mol Toxicol,2022,36(2):e22951.
SHAO M,LV D,ZHOU K,et al.Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway[J].Pharm Biol,2022,60(1):535-542.
YAN W,YU H,LIU B,et al.Andrographolide suppresses osteoarthritis progression by regulating circ_Rapgef1/miR-383-3p/NLRP3 signaling axis[J].Transpl Immunol,2022,71:101548.
ZHANG M,WU D,XU J,et al.Suppression of NLRP3 inflammasome by dihydroarteannuin via the HIF-1α and JAK3/STAT3 signaling pathway contributes to attenuation of collagen-induced arthritis in mice[J].Front Pharmacol,2022,13:884881.
MENG X,ZHANG X,SU X,et al.Daphnes Cortex and its licorice-processed products suppress inflammation via the TLR4/NF-κB/NLRP3 signaling pathway and regulation of the metabolic profile in the treatment of rheumatoid arthritis[J].J Ethnopharmacol,2022,283:114657.
LI W,WANG K,LIU Y,et al.A novel drug combination of mangiferin and cinnamic acid alleviates rheumatoid arthritis by inhibiting TLR4/NF-κB/NLRP3 activation-induced pyroptosis[J].Front Immunol,2022,13:912933.
ZHAO Y,CHEN Y,WANG Z,et al.The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of rheumatoid arthritis chondrocytes through the ASIC1a/NLRP3 signaling pathway[J].Ann Transl Med,2022,10(3):145.
LIU M,MENG X,XUAN Z,et al.Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis[J].Pharm Biol,2022,60(1):846-853.
REN L,LI Q,LI H,et al.Polysaccharide extract from Isatidis Radix inhibits multiple inflammasomes activation and alleviate gouty arthritis[J].Phytother Res,2022,36(8):3295-3312.
HE M,HU C,CHEN M,et al.Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU[J].J Nat Med,2022,76(1):178-187.
王敬博,仲米存,杨坤,等.基于NLRP3通路研究青梅复方对急性痛风性关节炎的干预作用及机制[J].中国实验方剂学杂志,2022,28(18):70-76.
ZHOU G Q,CHEN G,YANG J,et al.Guizhi-Shaoyao-Zhimu decoction attenuates monosodium urate crystal-induced inflammation through inactivation of NF-κB and NLRP3 inflammasome[J].J Ethnopharmacol,2022,283:114707.
LIN X,SHAO T,HUANG L,et al.Simiao decoction alleviates gouty arthritis by modulating proinflammatory cytokines and the gut ecosystem[J].Front Pharmacol,2020,11:955.
WANG Z,ZHANG P,ZHAO Y,et al.Scutellarin protects against mitochondrial reactive oxygen species-dependent NLRP3 inflammasome activation to attenuate intervertebral disc degeneration[J].Front Bioeng Biotechnol,2022,10:883118.
WANG D,CAI X,XU F,et al.Ganoderic Acid A alleviates the degeneration of intervertebral disc via suppressing the activation of TLR4/NLRP3 signaling pathway[J].Bioengineered,2022,13(5):11684-11693.
CHEN T,LI P,QIU J,et al.Aloin regulates matrix metabolism and apoptosis in human nucleus pulposus cells via the TAK1/NF-κB/NLRP3 signaling pathway[J].Stem Cells Int,2022,2022:5865011.
ZHOU Y,CHEN Z,YANG X,et al.Morin attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of the TXNIP/NLRP3/Caspase-1/IL-1β signaling pathway[J].Biochem Biophys Res Commun,2021,559:106-112.
TANG K,SU W,HUANG C,et al.Notoginsenoside R1 suppresses inflammatory response and the pyroptosis of nucleus pulposus cells via inactivating NF-κB/NLRP3 pathways[J].Int Immunopharmacol,2021,101(Pt B):107866.
ZHAO F,GUO Z,HOU F,et al.Magnoflorine alleviates "M1" polarized macrophage-induced intervertebral disc degeneration through repressing the HMGB1/Myd88/NF-κB pathway and NLRP3 inflammasome[J].Front Pharmacol,2021,12:701087.
0
Views
23
下载量
3
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution