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1.陕西中医药大学,陕西 咸阳 712046
2.陕西中医药大学 附属医院,陕西 咸阳 712000
Published:20 June 2023,
Published Online:20 October 2022,
Received:23 July 2022,
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李鑫,雷根平,冯喆等.基于足细胞损伤探讨中医药干预膜性肾病研究进展[J].中国实验方剂学杂志,2023,29(12):257-264.
LI Xin,LEI Genping,FENG Zhe,et al.Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):257-264.
李鑫,雷根平,冯喆等.基于足细胞损伤探讨中医药干预膜性肾病研究进展[J].中国实验方剂学杂志,2023,29(12):257-264. DOI: 10.13422/j.cnki.syfjx.20221905.
LI Xin,LEI Genping,FENG Zhe,et al.Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):257-264. DOI: 10.13422/j.cnki.syfjx.20221905.
膜性肾病是一类以肾小球足细胞损伤为核心机制的自身免疫性肾脏病,是成人肾病综合征常见的病理类型,已成为我国终末期肾脏病的主要病因。足细胞为终末分化细胞,在维持肾小球结构和功能稳定方面具有重要的作用,是蛋白滤过的分子屏障。足细胞损伤,从而肾小球滤过膜损伤是导致大量蛋白尿的重要原因,蛋白尿持续或加重使得膜性肾病患者病程迁延不愈。目前认为膜性肾病的足细胞破坏主要与氧化应激、自噬失调、足细胞标志蛋白表达异常、慢性炎症、上皮-间充质细胞转分化等存在密切联系。现阶段西医多依据其病理分期采用免疫抑制剂、激素类药物针对治疗,但存在一定的不良反应。中医药在防治膜性肾病上取得了一定成效,近年来,研究发现许多中药可通过作用于人体的多个靶点,在不同环节上影响膜性肾病的发生和发展具有明显的优势。该文概述了膜性肾病足细胞损伤的相关机制,并从中药单体及中药提取物、中药复方和中成药的角度干预相关靶点通路治疗膜性肾病进行总结,旨在为中医药抗膜性肾病的临床治疗、基础研究及靶向药物的研发提供一定的参考依据。
Membranous nephropathy, an autoimmune kidney disease with glomerular podocyte injury as the core mechanism, is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress, autophagy dysregulation, abnormal expression of podocyte marker proteins, chronic inflammation, epithelial-mesenchymal cell transdifferentiation, and so on. At present, western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage, but there are certain adverse reactions. Traditional Chinese medicine (TCM) has made some achievements in the prevention and treatment of membranous nephropathy. In recent years, studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body, with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers, compounds, and Chinese patent medicines in intervening related target pathways, aiming to provide a basis for the clinical treatment, basic research, and targeted drug development of TCM against membranous nephropathy.
膜性肾病足细胞发病机制中医药综述
membranous nephropathypodocytepathogenesistraditional Chinese medicinereview
RONCO P,BECK L,DEBIEC H,et al.Membranous nephropathy[J].Nat Rev Dis Primers,2021,7(1):69.
CAI Q,HENDRICKS A R.Membranous nephropathy: A ten-year journey of discoveries[J].Semin Diagn Pathol,2020,37(3):116-120.
XU X,WANG G,CHEN N,et al.Long-term exposure to air pollution and increased risk of membranous nephropathy in China[J].J Am Soc Nephrol,2016,27(12):3739-3746.
ROVIN B,ADLER S,BARRATT J,et al.KDIGO 2021 clinical practice guideline for the management of glomerular diseases[J].Kidney Int,2021,100(4S):S1-S276.
JIN J,ZHAN H,LIN B,et al.Association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy[J].Int Urol Nephrol,2017,49(6):1025-1031.
JALALAH S M.Podocytes intracytoplasmic dense inclusions: Are they associated with subepithelial dense deposits? An ultrastructural study[J].J Microsc Ultrastruct,2020,8(3):121-125.
周盈,宋子威,谢璇,等.中医对特发性膜性肾病发病机制的认识[J].中华中医药杂志,2020,35(11):5662-5664.
ICHIMURA K,MIYAKI T,KAWASAKI Y,et al.Morphological processes of foot process effacement in puromycin aminonucleoside nephrosis revealed by FIB/SEM tomography[J].J Am Soc Nephrol,2019,30(1):96-108.
LU C C,WANG G H,LU J,et al.Role of podocyte injury in glomerulosclerosis[J].Adv Exp Med Biol,2019,1165:195-232.
RONCO P,DEBIEC H.Molecular pathogenesis of membranous nephropathy[J].Annu Rev Pathol,2020,15:287-313.
金珍杰,何平.氧化应激在肾脏疾病发生发展中作用的研究进展[J].山东医药,2020,60(14):103-105.
KRATA N,FORONCEWICZ B,ZAGOŻDŻON R,et al.Peroxiredoxins as markers of oxidative stress in IgA nephropathy, membranous nephropathy and lupus nephritis[J].Arch Immunol Ther Exp (Warsz),2021,70(1):3.
ZHANG J,WANG X,VIKASH V,et al.ROS and ROS-mediated cellular signaling[J].Oxid Med Cell Longev,2016,2016:4350965.
陈朝红,刘志红,洪亦眉,等.雷公藤甲素干预C5b-9诱导足细胞损伤的体外研究[J].肾脏病与透析肾移植杂志,2009,18(4):310-317.
KLIONSKY D J,ABDEL-AZIZ A K,ABDELFATAH S,et al.Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1)[J].Autophagy,2021,17(1):1-382.
吴洪銮,安宁,钟珍,等.自噬在膜性肾病补体攻膜复合物所致足细胞损伤中的作用[J].广东医科大学学报,2020,38(5):526-531.
ATWOOD D J,POKHREL D,BROWN C N,et al.Increased mTOR and suppressed autophagic flux in the heart of a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease[J].Cell Signal,2020,74:109730.
ROGACKA D,AUDZEYENKA I,PIWKOWSKA A.Regulation of podocytes function by AMP-activated protein kinase[J].Arch Biochem Biophys,2020,692:108541.
郝文霞,高飞,赵方,等.降脂通络软胶囊调控AMPK/mTOR信号通路对膜性肾病大鼠自噬的影响[J].中药药理与临床,2021,37(4):148-153.
李童,赵媛媛,杨发奋.足细胞标志蛋白在足细胞病中的研究进展[J].右江医学,2022,50(1):72-75.
ARTELT N,LUDWIG T A,ROGGE H,et al.The role of palladin in podocytes[J].J Am Soc Nephrol,2018,29(6):1662-1678.
DLUGOS C P,PICCIOTTO C,LEPA C,et al.Nephrin signaling results in integrin β1 activation[J].J Am Soc Nephrol,2019,30(6):1006-1019.
POZZI A,ZENT R.Integrins in kidney disease[J].J Am Soc Nephrol,2013,24(7):1034-1039.
OH J,REISER J,MUNDEL P.Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome[J].Pediatr Nephrol,2004,19(2):130-137.
SUTARIYA B,TANEJA N,SARAF M.Betulinic acid, isolated from the leaves of Syzygium cumini (L.) Skeels, ameliorates the proteinuria in experimental membranous nephropathy through regulating Nrf2/NF-κB pathways[J].Chem Biol Interact,2017,274:124-137.
GAO Y,DAI H,ZHANG N,et al.The ameliorative effect of Mahuang Fuzi and Shenzhuo decoction on membranous nephropathy of rodent model is associated with autophagy and Wnt/β-catenin pathway[J].Front Pharmacol,2022,13:820130.
ZHANG P,YU C,YU J,et al.Arid2-IR promotes NF-κB-mediated renal inflammation by targeting NLRC5 transcription[J].Cell Mol Life Sci,2021,78(5):2387-2404.
WAN Q,LIU Z,YANG M,et al.Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway[J].BMC Mol Cell Biol,2020,21(1):4.
SONG N,THAISS F,GUO L.NF-κB and kidney injury[J].Front Immunol,2019,10:815.
LIU B,LU R,LI H,et al.Zhen-wu-tang ameliorates membranous nephropathy rats through inhibiting NF-κB pathway and NLRP3 inflammasome[J].Phytomedicine,2019,59:152913.
LIU Y,XU X,XU R,et al.Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritis in experimental rat model through its anti-oxidative and anti-inflammatory properties[J].Drug Des Devel Ther,2019,13:3735-3751.
LI Y,KANG Y S,DAI C,et al.Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria[J].Am J Pathol,2008,172(2):299-308.
DOU Y,SHANG Y,SHEN Y,et al.Baicalin alleviates adriamycin-induced focal segmental glomerulosclerosis and proteinuria by inhibiting the Notch1-Snail axis mediated podocyte EMT[J].Life Sci,2020,257:118010.
LI Z,WANG F,ZHA S,et al.SIRT1 inhibits TGF-β-induced endothelial-mesenchymal transition in human endothelial cells with Smad4 deacetylation[J].J Cell Physiol,2018,233(11):9007-9014.
ZHENG R,DENG Y,CHEN Y,et al.Astragaloside Ⅳ attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway[J].Phytother Res,2012,26(6):892-898.
刘张红,程锦国,陈玲玲,等.加减补阳还五汤对膜性肾病大鼠TGF-β1、VEGF和MMP-9表达的影响[J].浙江中医杂志,2020,55(5):318-320.
刘玉旋,李平,梁昌昌,等.276例特发性膜性肾病中医证候分布及其影响因素分析[J].世界中医药,2022,17(22):3229-3234.
WANG N,WEI R B,LI Q P,et al.Protective effects of astragaloside in rats with adriamycin nephropathy and underlying mechanism[J].Chin J Nat Med,2016,14(4):270-277.
王宇晖,童孟立,杨汝春.黄芪甲苷联合大黄素通过Smads通路抑制TGF-β1诱导的足细胞凋亡[J].中华中医药学刊,2014,32(5):1089-1093.
LU R,CHEN J,LIU B,et al.Protective role of Astragaloside Ⅳ in chronic glomerulonephritis by activating autophagy through PI3K/Akt/AS160 pathway[J].Phytother Res,2020,34(12):3236-3248.
赵宏,高琪,孔令洲,等.车前子、牛膝配伍治疗膜性肾病的网络药理学研究[J].中药新药与临床药理,2020,31(11):1343-1349.
赵宏,陈晨,赵岩,等.车前子多糖对膜性肾病大鼠肾损伤和肠道菌群的影响[J].中国实验方剂学杂志,2021,27(22):92-99.
秦卫松,刘志红,曾彩虹,等.雷公藤甲素对Heymann肾炎模型足细胞病变的影响[J].肾脏病与透析肾移植杂志,2007,16(2):101-109.
WANG L,ZHANG L,HOU Q,et al.Triptolide attenuates protein-uria and Podocyte apoptosis via inhibition of NF-κB/GADD45B[J].Scientific Reports,2018,8(1):10843.
CHEN Z H,QIN W S,ZENG C H,et al.Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro[J].Kidney Int,2010,77(11):974-988.
ZHOU Y,HONG Y,HUANG H H.Triptolide attenuates inflam-matory response in membranous glomerulo nephritis rat via downregulation of NF-κB signaling pathway[J].Kidney Blood Press Res,2016,41(11):901-910.
李莉,张琼果,潘巧虹,等.基于胞外信号调节激酶/胞浆型磷脂酶A2信号通路分析川穹嗪对膜性肾病大鼠肾保护作用[J].中国临床药理学杂志,2020,36(12):1665-1668.
樊红卫,薛海燕,姚建辉,等.川芎嗪通过抑制NF-κB信号通路减轻膜性肾病大鼠的炎症反应和肾脏损伤[J].药物评价研究,2021,44(8):1666-1673.
王玉洁,曹灵,胡承刚,等.川芎嗪对膜性肾病的治疗作用及对内质网应激的拮抗[J].中药材,2021,44(5):1213-1218.
张燕.膜性肾病大鼠足细胞转分化情况及川芎嗪对其影响的实验研究[D].泸州:泸州医学院,2011.
洪涛,崔路可,文集,等.虫草素对补体复合物介导的足细胞损伤的保护作用[J].四川大学学报:医学版,2015,46(2):173-178,227.
林劲,欧阳辉,梁春玲,等.白芍总苷对膜性肾病大鼠肾脏保护作用及自噬的影响[J].中药新药与临床药理,2019,30(9):1025-1031.
梁舜禹.原苏木素A对C5b-9介导下足细胞损伤的保护作用及其蛋白质组学研究[D].哈尔滨:黑龙江省中医药科学院,2019.
林宜,孙玥,谭建平,等.青藤碱对Heymann肾炎大鼠足细胞损伤的干预作用及机制研究[J].浙江医学,2021,43(9):924-929,后插1.
陈钦,吴亚琴,赵静雅,等.水蛭素对被动型Heymann肾炎模型大鼠足细胞Nephrin表达的影响[J].中国中西医结合肾病杂志,2017,18(12):1041-1045,后插1.
冯振伟,陈圳炜,杨陈,等.方格星虫提取物对膜性肾病模型的治疗作用及机制初探[J].中国中西医结合肾病杂志,2012,13(3):219-222,后插5.
WANG Z,LIU J,SUN W.Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal slit diaphragm proteins in adriamycin-induced rat nephropathy[J].Life Sci,2013,93(8):352-358.
王竹,孙万森,刘俊田.积雪草苷对足细胞α-actinin-4、synaptopodin蛋白及ERK/JNK通路的影响[J].西部中医药,2021,34(7):23-29.
孔怡然,杨凤文,任美芳,等.益肾通络方对膜性肾病大鼠足细胞表型转化的影响[J].中华中医药学刊,2020,38(4):233-236,后插26-26后插28.
陈素枝,臧倩男,张卓,等.益肾通络方对膜性肾病大鼠的肾保护作用及足细胞骨架相关蛋白的影响[J].中草药,2018,49(20):4857-4863.
张欣欣,高飞,陈素枝,等.益肾通络方对膜性肾病大鼠的肾保护作用及对AMPK/mTOR/ULK1信号通路的影响[J].中国实验方剂学杂志,2021,27(12):57-66.
高飞,王泽泽,杨冰,等.加味升降散对膜性肾病大鼠PI3K/Akt/mTOR信号通路及自噬的影响[J].中国实验方剂学杂志,2020,26(20):25-31.
李绍慧,高飞,郝文霞,等.加味升降散调控HIF-1α/NOX4信号通路对膜性肾病大鼠氧化应激和凋亡的影响[J].中国实验方剂学杂志,2021,27(19):66-72.
邵建彬,王霞,徐华洲,等.芪苓通络方抑制TLR4/MyD88/NF-κB信号通路改善特发性膜性肾病大鼠肾损伤[J].中国实验方剂学杂志,2022,28(4):100-108.
赵亚云,方敬,陈静洁,等.三焦祛湿方对C-BSA诱导膜性肾病小鼠肾脏保护作用及其对Nrf2/HO-1信号通路的影响[J].中国实验方剂学杂志,2021,27(18):58-65.
赵亚云,方敬,刘海平,等.基于NOX4/ROS/p38信号通路探讨三焦祛湿方对膜性肾病小鼠的抗氧化应激作用[J].中草药,2022,53(4):1076-1083.
邢建月,王世荣,刘光珍,等.芪龙通肾方治疗膜性肾病大鼠蛋白尿的作用机制研究[J].中国药物与临床,2021,21(1):14-17.
陈玲玲,程锦国,张良,等.益气活血化瘀汤对膜性肾病大鼠肾脏组织Nephrin mRNA和Podocin mRNA表达的影响[J].上海中医药杂志,2018,52(10):87-91.
宋越,张承承,姜韩雪,等.疏利分消方调控自噬对补体攻膜复合物所致足细胞损伤的内在机制研究[J].中国中西医结合肾病杂志,2021,22(1):11-13,后插1.
郭晓媛,蔡月茹,孙广宇,等.扶正祛风方对膜性肾病大鼠蛋白尿及肾脏病理改变的影响[J].中国实验方剂学杂志,2018,24(1):136-141.
郭晓媛,雷明,宋子威,等.扶正祛风方通过TGF-β1/Smad信号通路抑制膜性肾病大鼠足细胞转分化的机制[J].中国实验方剂学杂志,2021,27(8):57-65.
李静静.基于PI3K/Akt/mTOR通路探讨芪地固肾片对IMN大鼠肾组织的保护机制[D].咸阳:陕西中医药大学,2020.
赵方,高飞,李绍慧,等.降脂通络软胶囊调控SIRT1/FoxO3通路对膜性肾病大鼠细胞凋亡的影响[J].中国实验方剂学杂志,2022,28(7):113-120.
徐爱华,徐冬梅.黄葵胶囊联合依那普利治疗特发性膜性肾病低危患者的疗效评价[J].医学理论与实践,2021,34(1):59-61.
丁方睿,司南,边宝林,等.毛蕊花糖苷对嘌呤霉素肾病及足细胞损伤模型的疗效研究[J].中华肾脏病杂志,2018,34(1):30-35.
司瑞花,贾世艳,侯彦婕,等.基于p38 MAPK信号通路探讨复方蛇龙胶囊对膜性肾病大鼠的作用[J].中国实验方剂学杂志,2022,28(9):88-96.
WANG X,LIU J,TIAN R,et al.Sanqi oral solution mitigates proteinuria in rat passive heymann nephritis and blocks podocyte apoptosis via Nrf2/HO-1 pathway[J].Front Pharmacol,2021,19(12):727874.
蔡小凡,邓跃毅,钟逸斐,等.参芪膜肾颗粒对膜性肾病大鼠的治疗作用及机制初探[J].中国中西医结合肾病杂志,2017,18(10):852-855,后插1.
李小会,赵容,陈丽名,等.黄菟益肾颗粒对特发性膜性肾病肾病综合征疗效及对Th17/Treg免疫失衡的影响[J].辽宁中医药大学学报,2022,24(9):1-5.
冯喆,雷根平,王婷,等.芪地固肾片对膜性肾病大鼠的肾保护作用[J].中成药,2021,43(11):3166-3171.
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