阿霉素肾病模型及其病理机制研究进展
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摘要
阿霉素肾病模型是目前公认的能够较好模拟人类肾病的模型之一,其动物模型的表现类似于临床的人类肾病综合征,其细胞模型因能够较好地模拟肾小球足细胞的基本功能而广泛应用于肾病的病理机制研究。从阿霉素肾病的动物模型和体外细胞模型入手,旨在系统地阐述阿霉素肾病模型的造模方法和病理机制,为基于肾脏疾病的药物研发提供科学、合理的药理学实验模型参考,为开展中药复方治疗肾病的作用机制研究提供依据。
Adriamycin-induced nephritic model is one of the well-recognized models in simulating human nephropathy, whose clinical manifestations of animal models are similar to human nephrotic syndrome, and its cell models are widely used in the pathological mechanism study of nephropathy because of the well-simulated basic function of glomerular podocyte. Based on the animal models and cell models in vitro of adriamycin nephropathy, this study aims at reviewing the modelling method and pathological mechanism of adriamycin-induced nephritic model in order to provide a scientific and rational pharmacological experimental model reference for drug research and development based on kidney disease, and provide evidence for the research of the mechanism of Chinese herbal compound in the treatment of nephropathy.
Adriamycin-induced nephritic model is one of the well-recognized models in simulating human nephropathy, whose clinical manifestations of animal models are similar to human nephrotic syndrome, and its cell models are widely used in the pathological mechanism study of nephropathy because of the well-simulated basic function of glomerular podocyte. Based on the animal models and cell models in vitro of adriamycin nephropathy, this study aims at reviewing the modelling method and pathological mechanism of adriamycin-induced nephritic model in order to provide a scientific and rational pharmacological experimental model reference for drug research and development based on kidney disease, and provide evidence for the research of the mechanism of Chinese herbal compound in the treatment of nephropathy.
引文
[1]马迪.浅谈中医对肾病综合征发病机理的认识[A]//吉林省第四届科学技术学术年会论文集(下册)[C].长春:吉林省科学技术协会,2006.
[2]Wolf G,Ziyadeh F N.Molecular mechanisms of diabetic renal hypertrophy[J].Kidney Int,1999,56(2):393-405.
[3]赛依帕,宋元春,高霞,等.黄芪总苷对阿霉素诱导的足细胞损伤的保护作用[J].中药药理与临床,2017,33(3):70-73.
[4]Lee V W S,Harris D C.Adriamycin nephropathy:Amodel of focal segmental glomerulosclerosis[J].Nephrology,2011,16(1):30-38.
[5]Wang Y,Wang Y P,Tay Y C,et al.Progressive adriamycin nephropathy in mice:sequence of histologic and immunohistochemical events[J].Kidney Int,2000,58(4):1797-1804.
[6]Sonneveld R,FerrèS,Hoenderop J G J,et al.Vitamin Ddown-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease[J].Am J Pathol,2013,182(4):1196-1204.
[7]Chen X P,Lei F Y,Qin Y H,et al.The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury[J].J Recep Signal Transd,2014,34(6):484-492.
[8]Bertani T,Poggi A,Pozzoni R,et al.Adriamycin-induced nephrotic syndrome in rats:sequence of pathologic events[J].Lab Invest,1982,46(1):16-23.
[9]刘俊朝,和永瑞,薛媛媛,等.青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化[J].中国中西医结合儿科学,2016,8(4):383-386.
[10]Zan J,Shen C,Zhang L,et al.Effect of Poria cocos hydroethanolic extract on treating adriamycin-induced rat model of nephrotic syndrome[J].Chin J Integr Med,2017,23(12):916-922.
[11]Kunitomo M,Yamaguchi Y,Matsushima K,et al.Hyperlipidemic effects of adriamycin in rats[J].Jpn JPharmacol,1985,39(3):323-329.
[12]Liu G,Wang Q,Shi Y,et al.Resveratrol attenuates adriamycin-induced focal segmental glomerulosclerosis through C3aR/C5aR-sphingosine kinase 1 pathway[J].Pharmacology,2017,100(5/6):253-260.
[13]Amore A,Mazzucco G,Cavallo F,et al.Adriamycin-induced proteinuria in nude mice:An immune-system-mediated toxic effect[J].Nephrol Dial Transplant,1996,11(6):1012-1018.
[14]Zheng Z,Schmidtott K M,Chua S,et al.A mendelian locus on chromosome 16determines susceptibility to doxorubicin nephropathy in the mouse[J].Proc Natl Acad Sci USA,2005,102(7):2502-2507.
[15]De B E,Navis G,Tiebosch A T,et al.Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats[J].J Am Soc Nephrol,1999,10(11):2359-2366.
[16]Liu G,Shi Y,Peng X,et al.Astaxanthin attenuates adriamycin-induced focal segmental glomerulosclerosis[J].Pharmacology,2015,95(3/4):193-200.
[17]Hussein A M,Eldosoky M,Handhle A,et al.Effects of long-acting erythropoietin analog darbepoetin-αon adriamycin-induced chronic nephropathy[J].Int Urol Nephrol,2016,48(2):287-297.
[18]Fernández-Llama P,Andrews P,Nielsen S,et al.Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome[J].Kidney Int,1998,53(5):1244-1253.
[19]李爱平,张王宁,秦雪梅.阿霉素肾病大鼠模型的优化[J].中草药,2018,49(1):151-159.
[20]杨维娜,于琳华,郭尚温,等.改良阿霉素肾病大鼠模型的建立[J].西安交通大学学报:医学版,2009,30(4):445-448.
[21]蔺建军,杨勇,高娜,等.阿霉素注射次数及剂量对肾病综合征模型的影响[J].中国中西医结合肾病杂志,2011,12(8):676-678.
[22]Tacar O,Sriamornsak P,Dass C R.Doxorubicin:An update on anticancer molecular action,toxicity and novel drug delivery systems[J].J Pharm Pharmacol,2013,65(2):157-170.
[23]梁春玲.miRNA与AQP2在真武汤治疗阿霉素肾病综合征中的作用机理研究[D].广州:广州中医药大学,2016.
[24]张勇,张蓓,宁华英,等.单次尾静脉注射法阿霉素大鼠肾病模型的建立[J].中国实验动物学报,2013,21(1):1-4.
[25]Liu S,Jia Z,Zhou L,et al.Nitro-oleic acid protects against adriamycin-induced nephropathy in mice[J].Am J Physiol,2013,305(11):F1533-F1541.
[26]张王宁,李爱平,刘少博,等.基于代谢组学的阿霉素肾病大鼠模型损伤程度评价[J].中草药,2018,49(2):360-367.
[27]Jat P S,Noble M D,Ataliotis P,et al.Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58transgenic mouse[J].Proc Natl Acad Sci,1991,88(12):5096-5100.
[28]范青锋,丁洁.肾小球足细胞系的研究进展[J].中华实用儿科临床杂志,2005,20(1):71-72.
[29]Ohse T,Pippin J W,Vaughan M R,et al.Establishment of conditionally immortalized mouse glomerular parietal epithelial cells in culture[J].J Am Soc Nephrol,2008,19(10):1879-1890.
[30]Miao L,Wei D,Zhang Y,et al.Effects of stromal interaction molecule 1 or orai1 overexpression on the associated proteins and permeability of podocytes[J].Nephrology,2016,21(11):959-967.
[31]Yuan Y,Zhao C,An X,et al.A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton[J].Free Rad Res,2016,50(6):627-637.
[32]Li T,Mao J,Huang L,et al.Huaiqihuang may protect from proteinuria by resisting MPC5 podocyte damage via targeting p-ERK/CHOP pathway[J].Bosn J Basic Med Sci,2016,16(3):193-200.
[33]刘淑芳,丁洁,范青锋,等.嘌呤霉素致足细胞损伤细胞模型的建立[J].北京大学学报:医学版,2008,40(6):586-589.
[34]Miao L,Wei D,Zhang Y,et al.Effects of stromal interaction molecule 1 or Orai1 overexpression on the associated proteins and permeability of podocytes[J].Nephrology,2016,21(11):959-967.
[35]闫梦苗,刘光珍.复方蛇龙胶囊的拆方研究[J].时珍国医国药,2017,(10):2383-2385.
[36]Che R,Zhu C,Ding G,et al.Huaier cream protects against adriamycin-induced nephropathy by restoring mitochondrial function via PGC-1αupregulation[J].PPAR Res,2015,2015:720383.
[37]闫梦苗,刘光珍.阿霉素致足细胞损伤模型的建立[J].医学分子生物学杂志,2017,14(1):14-17.
[38]陈秀萍,覃远汉,雷凤英,等.全反式维甲酸受体在阿霉素致足细胞损伤中的表达及作用[J].广西医学,2014(5):556-560.
[39]Kestil?M,Lenkkeri U,M?nnikk?M,et al.Positionally cloned gene for a novel glomerular protein-nephrin-is mutated in congenital nephrotic syndrome[J].Mol Cell,1998,1(4):575-582.
[40]Boute N,Gribouval O,Roselli S,et al.NPHS2,encoding the glomerular protein podocin,is mutated in autosomal recessive steroid-resistant nephrotic syndrome[J].Nat Genet,2000,24(4):349-354.
[41]Donoviel D B,Freed D D,Vogel H,et al.Proteinuria and perinatal lethality in mice lacking NEPH1,a novel protein with homology to NEPHRIN[J].Mol Cell Biol,2001,21(14):4829-4836.
[42]Angst B D,Marcozzi C,Magee A I.The cadherin superfamily[J].J Cell Sci,2001,114(4):625-626.
[43]Lv Z,Hu M,Ren X,et al.Fyn mediates high glucose-induced actin cytoskeleton reorganization of podocytes via promoting ROCK activation in vitro[J].JDiabetes Res,2016,2016:5671803.
[44]Liu Y,Su L,Lin Q,et al.Induction of C-Mip by IL-17plays an important role in adriamycin-induced podocyte damage[J].Cell Physiol Biochem,2015,36(4):1274-1290.
[45]Zhang S,Kamal M,Dahan K,et al.C-mip impairs podocyte proximal signaling and induces heavy proteinuria[J].Sci Signal,2010,3(122):ra39.
[46]Akchurin O,Reidy K J.Genetic causes of proteinuria and nephrotic syndrome:Impact on podocyte pathobiology[J].Pediatr Nephrol,2015,30(2):221-233.
[47]V?lker L A,Petry M,Abdelsabour-Khalaf M,et al.Comparative analysis of Neph gene expression in mouse and chicken development[J].Histochem Cell Biol,2012,137(3):355-366.
[48]Hulkko J,Patrakka J,Lal M,et al.Neph1 is reduced in primary focal segmental glomerulosclerosis,minimal change nephrotic syndrome,and corresponding experimental animal models of adriamycin-induced nephropathy and puromycin aminonucleoside nephrosis[J].Nephron Extra,2014,4(3):146-154.
[49]Asanuma K,Yanagida-Asanuma E,Faul C,et al.Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling[J].Nat Cell Biol,2006,8(5):485-491.
[50]Guo N,Guo J,Su D.Micro RNA-206 and its down-regulation of Wilms’tumor-1 dictate podocyte health in adriamycin-induced nephropathy[J].Ren Fail,2016,38(6):989-995.
[51]马进,范志宏.整合素的研究进展[J].上海交通大学学报:医学版,2004,24(1):11-13.
[52]韩雯雯.α3β1整合素与足细胞病变[J].国际泌尿系统杂志,2015,35(5):787-790.
[53]Nicolaou N,Margadant C,Kevelam S H,et al.Gain of glycosylation in integrinα3 causes lung disease and nephrotic syndrome[J].J Clin Invest,2012,122(12):4375-4387.
[54]Jha J C,Banal C,Okabe J,et al.NADPH oxidase Nox5accelerates renal injury in diabetic nephropathy[J].Diabetes,2017,66(10):2691-2703.
[55]Kawamorita Y,Shiraishi T,Tamura Y,et al.Renoprotective effect of topiroxostat via antioxidant activity in puromycin aminonucleoside nephrosis rats[J].Physiol Rep,2017,5(15):e13358.
[56]Badary O A,Abdel-Naim A B,Abdel-Wahab M H,et al.The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats[J].Toxicology,2000,143(3):219-226.
[57]Tan R J,Zhou D,Xiao L,et al.Extracellular superoxide dismutase protects against proteinuric kidney disease[J].J Am Soc Nephrol,2015,26(10):24-47.
[58]Mo H,Wu Q,Miao J,et al.Chemokine receptor CXCR4plays a crucial role in mediating oxidative stress-induced podocyte injury[J].Antioxid Redox Signal,2015,17(2):S77.
[59]Yoshinari D,Takeyoshi I,Koibuchi Y,et al.Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats:involvement of the p38 mitogen-activated protein kinase pathway[J].Crit Care Med,2001,29(3):628-634.
[60]Furuichi K,Wada T,Iwata Y,et al.Administration of FR167653,a new anti-inflammatory compound,prevents renal ischaemia/reperfusion injury in mice[J].Nephrol Dial Transplant,2002,17(3):399-407.
[61]Li J,Campanale N V,Liang R J,et al.Inhibition of p38mitogen-activated protein kinase and transforming growth factor-β1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy[J].Am J Pathol,2006,169(5):1527-1540.
[62]Ge J,Miao J J,Sun X Y,et al.Huangkui capsule,an extract from Abelmoschus manihot(L.)medic,improves diabetic nephropathy via activating Peroxisome proliferator-activated receptor(PPAR)-α/γand attenuating endoplasmic reticulum stress in rats[J].JEthnopharmacol,2016,189:238-249.
[63]Daha M R,Van Kooten C.Is the proximal tubular cell a proinflammatory cell?[J].Nephrol Dial Transplant,2000,15(Suppl 6):41-43.
[64]Zhong F,Chen H,Han L,et al.Curcumin attenuates lipopolysaccharide-induced renal inflammation[J].Chin J Integr Tradit And West Nephrol,2009,34(2):226-232.
[65]Zhong F,Wang W M,Lee K,et al.Role of C/EBP-αin adriamycin-induced podocyte injury[J].Sci Rep,2016,6:33520.
[66]Vaziri N D,Wong J,Pahl M,et al.Chronic kidney disease alters intestinal microbial flora[J].Kidney Int,2013,83(2):308-315.
[67]Jiang Q,He X,Zou Y,et al.Altered gut microbiome promotes proteinuria in mice induced by adriamycin[J].AMB Express,2018,8(1):31.
[68]Fahim M A,Kataya H,El-Kharrag R,et al.Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin[J].World J Gastroenterol,2011,17(33):3836-3841.
[69]Bajaj J S,Ridlon J M,Hylemon P B,et al.Linkage of gut microbiome with cognition in hepatic encephalopathy[J].Am J Physiol,2016,302(1):168-175.
[70]Agrawal S,Zaritsky J J,Fornoni A,et al.Dyslipidaemia in nephrotic syndrome:Mechanisms and treatment[J].Nat Rev Nephrol,2017,14(1):70.
[71]Liang C,Wu J,Lai J,et al.Protection effect of Zhen-Wu-Tang on adriamycin-induced nephrotic syndrome via inhibiting oxidative lesions and inflammation damage[J].J Evidence-Based Compl Altern Med,2014,dio:10.1155/2014/131604.
[72]王海燕,李惊子,潘辑圣,等.中药黄芪当归合剂对肾病综合征肾损伤的保护作用及对代谢紊乱的影响[J].北京大学学报:医学版,2002,34(5):542-552.
[73]Wang Y,Gusarova V,Banfi S,et al.Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion[J].J Lipid Res,2015,56(7):1296-1307.
[74]王玉柱.血管生成素样蛋白3(ANGPTL3)与高脂血症性急性胰腺炎的相关性研究[D].郑州:郑州大学,2016.
[75]Liu J,Gao X,Zhai Y,et al.A novel role of angiopoietin-like-3 associated with podocyte injury[J].Pediatric Res,2015,77(6):732-739.
[76]Lin Y,Rao J,Zha X,et al.Angiopoietin-like 3 induces podocyte F-actin rearrangement through integrin/FAK/PI3K pathway-mediated rac1 activation[J].Biomed Res Inter,2013,2013:135608.
[77]Falke L L,Gholizadeh S,Goldschmeding R,et al.Diverse origins of the myofibroblast-implications for kidney fibrosis[J].Nat Rev Nephrol,2015,11(4):233-244.
[78]Guo Y,Xiao L,Sun L,et al.Wnt/beta-catenin signaling:A promising new target for fibrosis diseases[J].Physiol Res,2012,61(4):337-346.
[79]Sutariya B,Jhonsa D,Saraf M N.TGF-β:The connecting link between nephropathy and fibrosis[J].Immunopharmacol Immunotoxicol,2016,38(1):39-49.
[80]Greene I.Kaempferol and Esculetin as Potential Therapeutic Agents in Chronic Renal Allograft Injury[M].Mount Sinai:Icahn School of Medicine,2015.
[81]Jia L,Ma X,Gui B,et al.Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition[J].PLoS One,2015,10(2):e0117757.
[82]Liu W J,Luo M N,Tan J,et al.Autophagy activation reduces renal tubular injury induced by urinary proteins[J].Autophagy,2014,10(2):243-256.
[83]Button R W,Vincent J H,Strang C J,et al.Dual PI-3kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis[J].Oncotarget,2016,7(5):5157-5175.
[84]CinàD P,Onay T,Paltoo A,et al.Inhibition of MTORdisrupts autophagic flux in podocytes[J].J Am Soc Nephrol,2012,23(4):412-420.
[85]Nicolaou N,Margadant C,Kevelam S H,et al.Gain of glycosylation in integrinα3 causes lung disease and nephrotic syndrome[J].J Clin Invest,2012,122(12):4375-4387.
[86]Jiang L,Ding J,Tsai H,et al.Over-expressing transient receptor potential cation channel 6 in podocytes induces cytoskeleton rearrangement through increases of intracellular Ca2+and RhoA activation[J].Exp Biol Med,2011,236(2):184-193.
[87]M?ller C C,Wei C,Altintas M M,et al.Induction of TRPC6 channel in acquired forms of proteinuric kidney disease[J].J Am Soc Nephrol,2007,18(1):29-36.
[88]Wang Z,Wei X,Zhang Y,et al.NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury[J].Cell Physiol Biochem,2009,24(5/6):619-626.
[89]Schlo?ndorff J,del Camino D,Carrasquillo R,et al.TRPC6 mutations associated with focal segmental glomerulosclerosis cause constitutive activation of NFAT-dependent transcription[J].Am J Physiol,2009,296(3):C558-C569.
[90]Lee H S,Song C Y.Effects of TGF-beta on podocyte growth and disease progression in proliferative podocytopathies[J].Kidney Blood Press Res,2010,33(1):24-29.
[91]Yu L,Lin Q,Liao H,et al.TGF-β1 induces podocyte injury through Smad3-ERK-NF-κB pathway and Fyn-dependent TRPC6 phosphorylation[J].Cell Physiol Biochem,2011,26(6):869-878.
[92]Zhou L,Liu Y.Wnt/[beta]-catenin signalling and podocyte dysfunction in proteinuric kidney disease[J].Nat Rev Nephrol,2015,11(9):535-545.
[93]Zhou J,Yuan W J,Feng Y,et al.Down-regulation of Wt1activates Wnt/β-catenin signaling through modulating endocytic route of LRP6 in podocyte dysfunction in vitro[J].Cell Signalling,2015,27(9):1772-1780.
[94]Zhang H,Ren R,Du J,et al.AF1q contributes to adriamycin-induced podocyte injury by activating Wnt/β-catenin signaling[J].Kidney Blood Press Res,2017,42(5):794-803.
[2]Wolf G,Ziyadeh F N.Molecular mechanisms of diabetic renal hypertrophy[J].Kidney Int,1999,56(2):393-405.
[3]赛依帕,宋元春,高霞,等.黄芪总苷对阿霉素诱导的足细胞损伤的保护作用[J].中药药理与临床,2017,33(3):70-73.
[4]Lee V W S,Harris D C.Adriamycin nephropathy:Amodel of focal segmental glomerulosclerosis[J].Nephrology,2011,16(1):30-38.
[5]Wang Y,Wang Y P,Tay Y C,et al.Progressive adriamycin nephropathy in mice:sequence of histologic and immunohistochemical events[J].Kidney Int,2000,58(4):1797-1804.
[6]Sonneveld R,FerrèS,Hoenderop J G J,et al.Vitamin Ddown-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease[J].Am J Pathol,2013,182(4):1196-1204.
[7]Chen X P,Lei F Y,Qin Y H,et al.The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury[J].J Recep Signal Transd,2014,34(6):484-492.
[8]Bertani T,Poggi A,Pozzoni R,et al.Adriamycin-induced nephrotic syndrome in rats:sequence of pathologic events[J].Lab Invest,1982,46(1):16-23.
[9]刘俊朝,和永瑞,薛媛媛,等.青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化[J].中国中西医结合儿科学,2016,8(4):383-386.
[10]Zan J,Shen C,Zhang L,et al.Effect of Poria cocos hydroethanolic extract on treating adriamycin-induced rat model of nephrotic syndrome[J].Chin J Integr Med,2017,23(12):916-922.
[11]Kunitomo M,Yamaguchi Y,Matsushima K,et al.Hyperlipidemic effects of adriamycin in rats[J].Jpn JPharmacol,1985,39(3):323-329.
[12]Liu G,Wang Q,Shi Y,et al.Resveratrol attenuates adriamycin-induced focal segmental glomerulosclerosis through C3aR/C5aR-sphingosine kinase 1 pathway[J].Pharmacology,2017,100(5/6):253-260.
[13]Amore A,Mazzucco G,Cavallo F,et al.Adriamycin-induced proteinuria in nude mice:An immune-system-mediated toxic effect[J].Nephrol Dial Transplant,1996,11(6):1012-1018.
[14]Zheng Z,Schmidtott K M,Chua S,et al.A mendelian locus on chromosome 16determines susceptibility to doxorubicin nephropathy in the mouse[J].Proc Natl Acad Sci USA,2005,102(7):2502-2507.
[15]De B E,Navis G,Tiebosch A T,et al.Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats[J].J Am Soc Nephrol,1999,10(11):2359-2366.
[16]Liu G,Shi Y,Peng X,et al.Astaxanthin attenuates adriamycin-induced focal segmental glomerulosclerosis[J].Pharmacology,2015,95(3/4):193-200.
[17]Hussein A M,Eldosoky M,Handhle A,et al.Effects of long-acting erythropoietin analog darbepoetin-αon adriamycin-induced chronic nephropathy[J].Int Urol Nephrol,2016,48(2):287-297.
[18]Fernández-Llama P,Andrews P,Nielsen S,et al.Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome[J].Kidney Int,1998,53(5):1244-1253.
[19]李爱平,张王宁,秦雪梅.阿霉素肾病大鼠模型的优化[J].中草药,2018,49(1):151-159.
[20]杨维娜,于琳华,郭尚温,等.改良阿霉素肾病大鼠模型的建立[J].西安交通大学学报:医学版,2009,30(4):445-448.
[21]蔺建军,杨勇,高娜,等.阿霉素注射次数及剂量对肾病综合征模型的影响[J].中国中西医结合肾病杂志,2011,12(8):676-678.
[22]Tacar O,Sriamornsak P,Dass C R.Doxorubicin:An update on anticancer molecular action,toxicity and novel drug delivery systems[J].J Pharm Pharmacol,2013,65(2):157-170.
[23]梁春玲.miRNA与AQP2在真武汤治疗阿霉素肾病综合征中的作用机理研究[D].广州:广州中医药大学,2016.
[24]张勇,张蓓,宁华英,等.单次尾静脉注射法阿霉素大鼠肾病模型的建立[J].中国实验动物学报,2013,21(1):1-4.
[25]Liu S,Jia Z,Zhou L,et al.Nitro-oleic acid protects against adriamycin-induced nephropathy in mice[J].Am J Physiol,2013,305(11):F1533-F1541.
[26]张王宁,李爱平,刘少博,等.基于代谢组学的阿霉素肾病大鼠模型损伤程度评价[J].中草药,2018,49(2):360-367.
[27]Jat P S,Noble M D,Ataliotis P,et al.Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58transgenic mouse[J].Proc Natl Acad Sci,1991,88(12):5096-5100.
[28]范青锋,丁洁.肾小球足细胞系的研究进展[J].中华实用儿科临床杂志,2005,20(1):71-72.
[29]Ohse T,Pippin J W,Vaughan M R,et al.Establishment of conditionally immortalized mouse glomerular parietal epithelial cells in culture[J].J Am Soc Nephrol,2008,19(10):1879-1890.
[30]Miao L,Wei D,Zhang Y,et al.Effects of stromal interaction molecule 1 or orai1 overexpression on the associated proteins and permeability of podocytes[J].Nephrology,2016,21(11):959-967.
[31]Yuan Y,Zhao C,An X,et al.A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton[J].Free Rad Res,2016,50(6):627-637.
[32]Li T,Mao J,Huang L,et al.Huaiqihuang may protect from proteinuria by resisting MPC5 podocyte damage via targeting p-ERK/CHOP pathway[J].Bosn J Basic Med Sci,2016,16(3):193-200.
[33]刘淑芳,丁洁,范青锋,等.嘌呤霉素致足细胞损伤细胞模型的建立[J].北京大学学报:医学版,2008,40(6):586-589.
[34]Miao L,Wei D,Zhang Y,et al.Effects of stromal interaction molecule 1 or Orai1 overexpression on the associated proteins and permeability of podocytes[J].Nephrology,2016,21(11):959-967.
[35]闫梦苗,刘光珍.复方蛇龙胶囊的拆方研究[J].时珍国医国药,2017,(10):2383-2385.
[36]Che R,Zhu C,Ding G,et al.Huaier cream protects against adriamycin-induced nephropathy by restoring mitochondrial function via PGC-1αupregulation[J].PPAR Res,2015,2015:720383.
[37]闫梦苗,刘光珍.阿霉素致足细胞损伤模型的建立[J].医学分子生物学杂志,2017,14(1):14-17.
[38]陈秀萍,覃远汉,雷凤英,等.全反式维甲酸受体在阿霉素致足细胞损伤中的表达及作用[J].广西医学,2014(5):556-560.
[39]Kestil?M,Lenkkeri U,M?nnikk?M,et al.Positionally cloned gene for a novel glomerular protein-nephrin-is mutated in congenital nephrotic syndrome[J].Mol Cell,1998,1(4):575-582.
[40]Boute N,Gribouval O,Roselli S,et al.NPHS2,encoding the glomerular protein podocin,is mutated in autosomal recessive steroid-resistant nephrotic syndrome[J].Nat Genet,2000,24(4):349-354.
[41]Donoviel D B,Freed D D,Vogel H,et al.Proteinuria and perinatal lethality in mice lacking NEPH1,a novel protein with homology to NEPHRIN[J].Mol Cell Biol,2001,21(14):4829-4836.
[42]Angst B D,Marcozzi C,Magee A I.The cadherin superfamily[J].J Cell Sci,2001,114(4):625-626.
[43]Lv Z,Hu M,Ren X,et al.Fyn mediates high glucose-induced actin cytoskeleton reorganization of podocytes via promoting ROCK activation in vitro[J].JDiabetes Res,2016,2016:5671803.
[44]Liu Y,Su L,Lin Q,et al.Induction of C-Mip by IL-17plays an important role in adriamycin-induced podocyte damage[J].Cell Physiol Biochem,2015,36(4):1274-1290.
[45]Zhang S,Kamal M,Dahan K,et al.C-mip impairs podocyte proximal signaling and induces heavy proteinuria[J].Sci Signal,2010,3(122):ra39.
[46]Akchurin O,Reidy K J.Genetic causes of proteinuria and nephrotic syndrome:Impact on podocyte pathobiology[J].Pediatr Nephrol,2015,30(2):221-233.
[47]V?lker L A,Petry M,Abdelsabour-Khalaf M,et al.Comparative analysis of Neph gene expression in mouse and chicken development[J].Histochem Cell Biol,2012,137(3):355-366.
[48]Hulkko J,Patrakka J,Lal M,et al.Neph1 is reduced in primary focal segmental glomerulosclerosis,minimal change nephrotic syndrome,and corresponding experimental animal models of adriamycin-induced nephropathy and puromycin aminonucleoside nephrosis[J].Nephron Extra,2014,4(3):146-154.
[49]Asanuma K,Yanagida-Asanuma E,Faul C,et al.Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling[J].Nat Cell Biol,2006,8(5):485-491.
[50]Guo N,Guo J,Su D.Micro RNA-206 and its down-regulation of Wilms’tumor-1 dictate podocyte health in adriamycin-induced nephropathy[J].Ren Fail,2016,38(6):989-995.
[51]马进,范志宏.整合素的研究进展[J].上海交通大学学报:医学版,2004,24(1):11-13.
[52]韩雯雯.α3β1整合素与足细胞病变[J].国际泌尿系统杂志,2015,35(5):787-790.
[53]Nicolaou N,Margadant C,Kevelam S H,et al.Gain of glycosylation in integrinα3 causes lung disease and nephrotic syndrome[J].J Clin Invest,2012,122(12):4375-4387.
[54]Jha J C,Banal C,Okabe J,et al.NADPH oxidase Nox5accelerates renal injury in diabetic nephropathy[J].Diabetes,2017,66(10):2691-2703.
[55]Kawamorita Y,Shiraishi T,Tamura Y,et al.Renoprotective effect of topiroxostat via antioxidant activity in puromycin aminonucleoside nephrosis rats[J].Physiol Rep,2017,5(15):e13358.
[56]Badary O A,Abdel-Naim A B,Abdel-Wahab M H,et al.The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats[J].Toxicology,2000,143(3):219-226.
[57]Tan R J,Zhou D,Xiao L,et al.Extracellular superoxide dismutase protects against proteinuric kidney disease[J].J Am Soc Nephrol,2015,26(10):24-47.
[58]Mo H,Wu Q,Miao J,et al.Chemokine receptor CXCR4plays a crucial role in mediating oxidative stress-induced podocyte injury[J].Antioxid Redox Signal,2015,17(2):S77.
[59]Yoshinari D,Takeyoshi I,Koibuchi Y,et al.Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats:involvement of the p38 mitogen-activated protein kinase pathway[J].Crit Care Med,2001,29(3):628-634.
[60]Furuichi K,Wada T,Iwata Y,et al.Administration of FR167653,a new anti-inflammatory compound,prevents renal ischaemia/reperfusion injury in mice[J].Nephrol Dial Transplant,2002,17(3):399-407.
[61]Li J,Campanale N V,Liang R J,et al.Inhibition of p38mitogen-activated protein kinase and transforming growth factor-β1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy[J].Am J Pathol,2006,169(5):1527-1540.
[62]Ge J,Miao J J,Sun X Y,et al.Huangkui capsule,an extract from Abelmoschus manihot(L.)medic,improves diabetic nephropathy via activating Peroxisome proliferator-activated receptor(PPAR)-α/γand attenuating endoplasmic reticulum stress in rats[J].JEthnopharmacol,2016,189:238-249.
[63]Daha M R,Van Kooten C.Is the proximal tubular cell a proinflammatory cell?[J].Nephrol Dial Transplant,2000,15(Suppl 6):41-43.
[64]Zhong F,Chen H,Han L,et al.Curcumin attenuates lipopolysaccharide-induced renal inflammation[J].Chin J Integr Tradit And West Nephrol,2009,34(2):226-232.
[65]Zhong F,Wang W M,Lee K,et al.Role of C/EBP-αin adriamycin-induced podocyte injury[J].Sci Rep,2016,6:33520.
[66]Vaziri N D,Wong J,Pahl M,et al.Chronic kidney disease alters intestinal microbial flora[J].Kidney Int,2013,83(2):308-315.
[67]Jiang Q,He X,Zou Y,et al.Altered gut microbiome promotes proteinuria in mice induced by adriamycin[J].AMB Express,2018,8(1):31.
[68]Fahim M A,Kataya H,El-Kharrag R,et al.Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin[J].World J Gastroenterol,2011,17(33):3836-3841.
[69]Bajaj J S,Ridlon J M,Hylemon P B,et al.Linkage of gut microbiome with cognition in hepatic encephalopathy[J].Am J Physiol,2016,302(1):168-175.
[70]Agrawal S,Zaritsky J J,Fornoni A,et al.Dyslipidaemia in nephrotic syndrome:Mechanisms and treatment[J].Nat Rev Nephrol,2017,14(1):70.
[71]Liang C,Wu J,Lai J,et al.Protection effect of Zhen-Wu-Tang on adriamycin-induced nephrotic syndrome via inhibiting oxidative lesions and inflammation damage[J].J Evidence-Based Compl Altern Med,2014,dio:10.1155/2014/131604.
[72]王海燕,李惊子,潘辑圣,等.中药黄芪当归合剂对肾病综合征肾损伤的保护作用及对代谢紊乱的影响[J].北京大学学报:医学版,2002,34(5):542-552.
[73]Wang Y,Gusarova V,Banfi S,et al.Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion[J].J Lipid Res,2015,56(7):1296-1307.
[74]王玉柱.血管生成素样蛋白3(ANGPTL3)与高脂血症性急性胰腺炎的相关性研究[D].郑州:郑州大学,2016.
[75]Liu J,Gao X,Zhai Y,et al.A novel role of angiopoietin-like-3 associated with podocyte injury[J].Pediatric Res,2015,77(6):732-739.
[76]Lin Y,Rao J,Zha X,et al.Angiopoietin-like 3 induces podocyte F-actin rearrangement through integrin/FAK/PI3K pathway-mediated rac1 activation[J].Biomed Res Inter,2013,2013:135608.
[77]Falke L L,Gholizadeh S,Goldschmeding R,et al.Diverse origins of the myofibroblast-implications for kidney fibrosis[J].Nat Rev Nephrol,2015,11(4):233-244.
[78]Guo Y,Xiao L,Sun L,et al.Wnt/beta-catenin signaling:A promising new target for fibrosis diseases[J].Physiol Res,2012,61(4):337-346.
[79]Sutariya B,Jhonsa D,Saraf M N.TGF-β:The connecting link between nephropathy and fibrosis[J].Immunopharmacol Immunotoxicol,2016,38(1):39-49.
[80]Greene I.Kaempferol and Esculetin as Potential Therapeutic Agents in Chronic Renal Allograft Injury[M].Mount Sinai:Icahn School of Medicine,2015.
[81]Jia L,Ma X,Gui B,et al.Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition[J].PLoS One,2015,10(2):e0117757.
[82]Liu W J,Luo M N,Tan J,et al.Autophagy activation reduces renal tubular injury induced by urinary proteins[J].Autophagy,2014,10(2):243-256.
[83]Button R W,Vincent J H,Strang C J,et al.Dual PI-3kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis[J].Oncotarget,2016,7(5):5157-5175.
[84]CinàD P,Onay T,Paltoo A,et al.Inhibition of MTORdisrupts autophagic flux in podocytes[J].J Am Soc Nephrol,2012,23(4):412-420.
[85]Nicolaou N,Margadant C,Kevelam S H,et al.Gain of glycosylation in integrinα3 causes lung disease and nephrotic syndrome[J].J Clin Invest,2012,122(12):4375-4387.
[86]Jiang L,Ding J,Tsai H,et al.Over-expressing transient receptor potential cation channel 6 in podocytes induces cytoskeleton rearrangement through increases of intracellular Ca2+and RhoA activation[J].Exp Biol Med,2011,236(2):184-193.
[87]M?ller C C,Wei C,Altintas M M,et al.Induction of TRPC6 channel in acquired forms of proteinuric kidney disease[J].J Am Soc Nephrol,2007,18(1):29-36.
[88]Wang Z,Wei X,Zhang Y,et al.NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury[J].Cell Physiol Biochem,2009,24(5/6):619-626.
[89]Schlo?ndorff J,del Camino D,Carrasquillo R,et al.TRPC6 mutations associated with focal segmental glomerulosclerosis cause constitutive activation of NFAT-dependent transcription[J].Am J Physiol,2009,296(3):C558-C569.
[90]Lee H S,Song C Y.Effects of TGF-beta on podocyte growth and disease progression in proliferative podocytopathies[J].Kidney Blood Press Res,2010,33(1):24-29.
[91]Yu L,Lin Q,Liao H,et al.TGF-β1 induces podocyte injury through Smad3-ERK-NF-κB pathway and Fyn-dependent TRPC6 phosphorylation[J].Cell Physiol Biochem,2011,26(6):869-878.
[92]Zhou L,Liu Y.Wnt/[beta]-catenin signalling and podocyte dysfunction in proteinuric kidney disease[J].Nat Rev Nephrol,2015,11(9):535-545.
[93]Zhou J,Yuan W J,Feng Y,et al.Down-regulation of Wt1activates Wnt/β-catenin signaling through modulating endocytic route of LRP6 in podocyte dysfunction in vitro[J].Cell Signalling,2015,27(9):1772-1780.
[94]Zhang H,Ren R,Du J,et al.AF1q contributes to adriamycin-induced podocyte injury by activating Wnt/β-catenin signaling[J].Kidney Blood Press Res,2017,42(5):794-803.