肾炎消白颗粒对阿霉素肾病大鼠肾小球足细胞NEPHRIN表达的影响
|
摘要
目的:探讨肾炎消白颗粒减少阿霉素肾病大鼠蛋白尿的作用,并从生化、分子生物学角度探讨其作用机理,为临床应用提供理论依据。
方法:60只Wistar大鼠,随机分为5组,分别为空白对照组、模型对照组、洛汀新组、肾炎消白颗粒低剂量组、肾炎消白颗粒高剂量组,用尾静脉一次性注射阿霉素制备肾炎蛋白尿模型,而后各组以预定方法灌胃,观察7周,于灌胃前一天及以后每七天检测大鼠的尿肌酐,酶联免疫法检测尿白蛋白,第七周末ELISA法检测尿β2-MG,免疫组织化学法检测大鼠肾组织中Nephrin蛋白表达情况。
结果:实验7周末各治疗组(肾炎消白颗粒高、低剂量组及洛汀新组)阿霉素肾病大鼠尿白蛋白/尿肌酐值下降,以肾炎消白颗粒高剂量组最为明显(P<0.05);尿β2-MG的含量降低,以肾炎消白颗粒高剂量组最为明显(P 结论:肾炎消白颗粒能够在一定程度上减少阿霉素肾病大鼠尿蛋白的排泄量;减少阿霉素肾病大鼠尿β2-MG的含量,对肾小管有保护作用;增加阿霉素肾病大鼠Nephrin在肾组织中的表达,对肾脏纤维化有治疗作用;中药高剂量组对于上述作用较中药低剂量组、洛汀新组疗效较好。
Objective:To test if nephritis Xiaobaikeli decreases proteinuria level in experimental animals and investigate its mechanism by biochemical and molecular biological analysis to provide the basis for its clinical application.
Methods:We utilized a rat model in which nephritis is induced by one-time tail vein injection of doxorubicin.Animals were divided into five groups,namely the naive control group,model control group,Lotensin group,low-dose nephritis Xiaobaikeli group and high-dose nephritis Xiaobaikeli group.Seven weeks after treatment,we detected rat urine creatinine,urine Scr,urineβ2-MG(by ELISA),proteinuria,Nephrin expression in kidney(by immunohistochemical staining),.
Results:At the end of 7-week observation,the ratio of proteinuria/urine creatinine values(P<0.05)were reduced in animals from all treatment group with doxorubicin-induced nephritis,and the high-dose nephritis Xiaobaikeli treatment had the most significant effects(P Conclusion:nephritis Xiaobaikeli can reduce excretion a certain extent,decrease urineβ2-MG level in nephrotic rats and protect tubulo: It can increase Nephrin expression in kidney tissues. The therapeutic effects with high-dose nephritis Xiaobaikeli are better than low-dose nephritis Xiaobaikeli or Lotensin.
方法:60只Wistar大鼠,随机分为5组,分别为空白对照组、模型对照组、洛汀新组、肾炎消白颗粒低剂量组、肾炎消白颗粒高剂量组,用尾静脉一次性注射阿霉素制备肾炎蛋白尿模型,而后各组以预定方法灌胃,观察7周,于灌胃前一天及以后每七天检测大鼠的尿肌酐,酶联免疫法检测尿白蛋白,第七周末ELISA法检测尿β2-MG,免疫组织化学法检测大鼠肾组织中Nephrin蛋白表达情况。
结果:实验7周末各治疗组(肾炎消白颗粒高、低剂量组及洛汀新组)阿霉素肾病大鼠尿白蛋白/尿肌酐值下降,以肾炎消白颗粒高剂量组最为明显(P<0.05);尿β2-MG的含量降低,以肾炎消白颗粒高剂量组最为明显(P
Objective:To test if nephritis Xiaobaikeli decreases proteinuria level in experimental animals and investigate its mechanism by biochemical and molecular biological analysis to provide the basis for its clinical application.
Methods:We utilized a rat model in which nephritis is induced by one-time tail vein injection of doxorubicin.Animals were divided into five groups,namely the naive control group,model control group,Lotensin group,low-dose nephritis Xiaobaikeli group and high-dose nephritis Xiaobaikeli group.Seven weeks after treatment,we detected rat urine creatinine,urine Scr,urineβ2-MG(by ELISA),proteinuria,Nephrin expression in kidney(by immunohistochemical staining),.
Results:At the end of 7-week observation,the ratio of proteinuria/urine creatinine values(P<0.05)were reduced in animals from all treatment group with doxorubicin-induced nephritis,and the high-dose nephritis Xiaobaikeli treatment had the most significant effects(P
引文
1.Hecg JE,De Jong PE,Van der Hern GK et al.Efficaey and variability of the antiproteinuric effect of ACE inhibition by lisinipril. Kidney Int,1989,36:272
2.Gansevoort R,de Zeeuw D,de Jong PE.Long-terin benefts of the antiproteinuric effect of ungiotensin-eonverting enzyme inhibition in nondiabetin renal diseases.AM J Kidney Dis,1993,22:202
3.Lewis EJ,Hunsicker L,Bain RP et al.For the Collaborative Study Group:The effect of angiotensin-converting-enayme inhibition on diabetic nephropathy.N Engl J Med,1993,329:1456
4.Jafar TH,Schnid CH,Landa M et al.Angiotensin-converting enzyme inhibition and progression of nondiabetic renal disease.A meta-analysis of patient-level data.Ann Intern Med,2001,135:73
5.仝小林,张志远.蛋白尿的中医治疗.中国医药学报[J],2002,17(2):115
6.刘伟,贝岩.中药辨证治疗蛋白尿探析.辽宁中医杂志[J],2005,32(3):225
7.郭立中,毛炜,刘玉宁,等.叶传惠教授对肾炎蛋白尿的病机认识及治疗经验.中国中西医结合肾病杂志[J],2001,2(3):128
8.李亦聪,冯天保.谢桂权教授治疗慢性肾炎蛋白尿经验介绍.新中医[J],2006,38(4):16
9.沈庆法.肾脏病蛋白尿的中医论治.中国临床医生[J],2004,32(8):50
10.金劲松.邵朝弟教授治疗蛋白尿的经验.中国中西医结合肾病杂志[J],2006,7(9):501
11.张琼.黄淑芬从络病论治肾性蛋白尿.中医杂志[J],2004,46(10):745
12.邓聪.从风郁瘀论治蛋白尿.中华中医药杂志[J],2006,21(8):506
13.沈庆法.清利法治疗蛋白尿.上海中医药杂志[J],2006,40(2):23
14.袁红霞,林嫦娥.黄文政教授治疗顽固性蛋白尿经验总结.天津中医药[J],2003,20(5):18-19
15.刘宏伟,王国栋,张国强.国医匠时振声教授学术贡献撷萃.中医药学刊[J],2001,19(6):534
16.杜秋霞.叶传惠教授诊治肾性蛋白尿经验.四川中医[J],2001,19(5):4
17.黄臻,邹嘉玉.皮持衡治疗单纯肾性蛋白尿的经验.江西中医药[J],2006,(37)284:6
18.陈瑜.中医辨治小儿慢性肾炎蛋白尿七法.中医研究[J],2001(14)5:30-31
19.庞莉.刘莉.周保林.贺永清主任医师治疗蛋白尿的经验.现代中医药[J],2005,3:22-23
20.邹玺,熊宁宁.长期应用清热利湿和络法对慢性肾炎患者蛋白尿变化的影响.中医杂志[J], 2004,45(4):266-269
21.方志传.养脾为主治疗慢性肾炎蛋白尿.湖北中医杂志[J],2001,23(8):346
22.张丽霞.升阳益气固肾化痪治疗慢性肾炎蛋白尿疗效观察.中医药学刊[J],2006,24(5):965-966
23.李玉花.活血化瘀法在蛋白尿治疗中的运用.实用中西医结合临床[J],2005,(5)2:55-56
24.王静.补肾固涩法为主治疗蛋白尿30例.陕西中医[J],2001,22(10):590
25.陈志强方敬刘丽等.青藤碱对系膜增生性肾小球肾炎影响的实验研究[J].中国老年学杂志,2007,27:27-28
26.刘志红,戴春笋,李恒等.雷公藤内酷醇对人近端肾小管上皮细胞单核细胞趋化因子合成的影响.肾脏病与透析肾移植杂志[J],2000,9(5):431-435
27.张万祥,秦建国,张荣等.参蔑益肾汤治疗疗肾性蛋白尿45例观察.时珍国医国药,2007,18(6):1482-1483
28.韩进庭.自拟消蛋白饮联合西药治疗蛋白尿30例.长春中医药大学学报,2007,23(4):59
29.刘永琴,刘淮阳.成人无症状性血尿蛋白尿的临床病理分析及预.四川医学[J],2002,23(1),32
30.尹莲芳,淮家伉,弓玉祥等.黄蜀葵花对阿霉素肾病大鼠钠储留改善作用的机制.中华肾脏病杂志[J].1999,15(5):324-325
31.杨俊伟,戴春笋,陈朝红等.雷公藤内酷醇对T细胞功能的影响与cAMP/PKA的关系.肾脏病与透析肾移植杂志[J],1998,7(2):106-112
32.黄黎明,梁恒,邢建宇等.山茱英提取物对慢性肾炎小鼠的药理作用及蛋白质组学效应的实验研究.中国药理学通报[J],2004,20(10):1144-1150
33.李宏伟,王荣欣.升阳益胃汤治疗慢性肾病蛋白尿42例.中国中医药科技,2001,8(3):161
34.吴金国,陈志龙,张黎明.急慢性肾炎中药治疗研究进展.中医药信息[J],2001,18(4):5
35.齐占华.益肾液治疗肾小球性蛋白尿疗效分析.实用中医药杂志[J],2005,21(10):585
36.梁汝钊.毛文忠.刘吉样.益肾煎治疗肾小球性蛋白尿31例.陕西中医[J],2005,26(8):753-754
37.练建红.刘恩棋.蒙向欣等.益肾I方治疗肾小球性蛋白尿的临床研究.福建中医药[J],2007,3(3):1-3
38.雷作熹,罗仁,董晓蕾等.小四五颗粒对糖尿病大鼠肾保护作用研究[J].中药新药与临床药理[J],2003,14(2):93-96
39.代方国,魏敏,孙晓敏等.小四五颗粒治疗慢性肾病蛋白尿30例临床观察[J].新中医,2007,39(8):33-34
40.何岚,王宁生.五苓散减轻阿霉素肾病大鼠蛋白尿的实验研究.中成药[J],2006,28(10):1532-1534
41.赵飞,王晓霞,程广清等.疏血通注射液治疗肾性蛋白尿69例临床观察[J].山东中医药大学学报,2007,31(4):294-295
42.Mundel P,Shankland SJ.Podocyte biology and resPonse toinjury.J Am Soe Neplirol,2002,13(12):3005-3015
43.Dustin ML,Olszowy MW,Holdorf AD,et al.A novella daptor protein or chestrates receptor Patterning and cytoskeletal polarity in T-cell contaets.Cell,1998,94(5):667-677
44.Shih NY,Li J,Karpitskii V,et al.Congenital nephritic syndrome in mice lacking CD2-assoeiated protein. Seienee,1999,286(5438):312-315
45.Pavenstadt H,Kriz W,Kretzler M.Cell biology of the glomerular podoeyte.Physiol Rev,2003,83(1):253-307
46.Coward RJ,Foster RR,Patton D,et al.Nephrotic plasma alters slit diaphragm dependent signaling and translocates nephrin,Podoein,and CD2 assoeiated protein in cultured human podoeytes.J Am Soc Nephrol,2005,16(3):629-637
47.Huber TB,Hardeben B,Kim J,et al.Nephrin and CD2AP associate with Phosphoinositide 3-OH kinase and stimulate AKT-dependent signaiing[J].MolCel lBiol,2003,23(14):4917-4928
48.Cantley LC.The phosphoinositide3-kinase pathway[J].Seienee,2002,296(5573):1655-1657
49. Wartiovaara J,Ofverstedt LG,Khoshnoodi J,et a1.Nephrin strands contribute to a porous slit diaphragm scafold as revealed by electron tomography.J Clin Invest,2004,114:1475-1483.
50.Beltcheva O,Martin P,Lenkkeri U,et a1.Mutation spectrum in the nephrin gene(NPHS1)in congenital nephritic syndrome.Hum Mutation,2001,17:368-373.
51.Verma R,Kovari I,Soofi A,et a1.Nephrin ectodomain engagement results in Src kinase activation,nephrin phosphorylation,Nek recruitment,and actin polymerization.J ClinInvest,2006,116:1346-1359.
52.Lahdenpera J , Kilpelainen P,Liu XL,et a1.Clustering-induced tymsine phosphorylation of nephrin by Src family kinases.Kidney Int,2003,64:404-413.
53.Kaplan JM,Kim SH,North KN, e tal.Mutations in ACTN4,encoding alpha-aetinin-4,cause familial foeal segmental glomerulaselerosis[J].Nat Genet,2000,24:251-256
54.Yao J,Le TC,Kos CH,et al.AIPha-actinin-4- mediated FSGS:an inherited kidney disease caused by an aggre-gated and rapidly degraded cytaskeletal protein[J] Plos Biol,2004,2(6):787-794
55.Weins A,Kenlan P,Herbert S,et al.Mutational and Bio-logieal Analysis of alpha-actinin-4 in focal segmental glomeruloselerosis[J].J Am Soe Nephrol.2005,16(12):3694-3701
56.何伟春,邢昌赢,孙彬等.CD2AP和α-actinin-4在大鼠阿霉素肾病模型中的表达.南京医科大学学报(自然科学版),2006,26(11):1005-1007
57.Boute N.Gribouval O.Roselli S.et al.NPHS2.encoding the gomerular protein Podoein,is mutated in autosomal recessive steroid- resistant nephritic syndrome.Nat Genet2000,24:349-354
58.Sehwarz K.Simons M.Keiser,J.et al.Podoein,araft-assoeiated component of the gomemlar slit diaphragm,interacts with CD2AP and nephrin.J Clin Invest,2001,108(11):1621-1629
59.Eiser J,Kriz W.The golmerular slit diaphragm is a modified adherens juntiln[J].J Am Sco Nephrol,2000,11(1):1
60.叶任高,沈清瑞.肾脏病诊断与治疗学.北京:北京人民卫生出版社[M],1994:208
61.叶任高,刘冠贤.临床肾脏病学.北京:北京人民卫生出版社[M],1997:52-53
62.林善琐,陈靖.肾小球疾病治疗最新进展.中国实用内科杂志,2000,20:26-29
63.Edited by Barry M.Brenner The kidneyy[J] .Science press sixth dition,2000,1271-1277
64.Albert Matalon,Anthong Valeri,and Grerald B Appel:Treatment of Focal segmental Glomerulosclerosis[J] .Seminars in Nephrology.2000,20:309-317
65.何敏华,叶任高,马翅云.糖皮质激素在肾小球疾病治疗中的进展.大理学院学报[J],2003,(2)3:52
66.李幼姬,叶任高,姜搅.成人原发性肾病综合征治疗的探索.中华肾脏病杂志[J],1995,11(3):133-136
67.黎磊石,张训,陈光永,等.雷公藤治疗肾小球肾炎的临床研究.中华内科杂志[J],1981,20(4):216
68.黎磊石,刘志红.雷公藤在肾脏病领域应用的前景.肾脏病与透析肾移植杂志[J],1997,6(3):203
69.施向东,范德墉,陆玉良.雷公藤多贰片对肾性蛋白尿的作用.中国中西医结合肾病杂志[J],2000,1(4),224-225
70.朱汉威,朱淳,陆玮,等.雷公藤多试长程治疗肾小球肾炎疗效观察.上海第二医科大学学报[J],2002,22(6):543-544
71.冯为盛,姜继元.霉酚酸酷治疗难治性肾病综合征.中华肾脏病杂志[J],1999,15(5):287
72.黄茂芹,周森,陈裕盛.霉酚酸酷治疗肾病综合征8例观察.中华肾脏病杂志[J],2000,16(6):386
73.刘光陵,高远斌,夏正坤,等.霉酚酸酷在小儿肾小球疾病治疗中的应用效果.中华儿科杂志[J],1999,37(10):640
74.沈平雁,蒋颈松.霉酚酸醋在治疗肾小球疾病中的应用.实用医学杂志[J],1999,15(9):731
75.Lou T,Wang C,Chen Z,et al.Randomised controlled trial of eflunomide in the treatment of immunoglobulin A nephropathy.Nephrology(Carlton),2006,11(2):113-116
76.王成,娄探奇,唐哗等.来氟米特治疗难治性肾病综合征60例临床研究.中国实用内科杂志[J],2005,25(12):1096-1095
77.崔太根,侯凡凡,倪兆慧,等.来氟米特联合糖皮质激素治疗增殖型狼疮性肾炎的多中心对照临床试验研究.中华内科杂志[J],2005,44(9):672-676
78.任岳钦,李延国,马云航.来氟米特治疗过敏性紫瘫性肾炎的临床研究.临床肾脏病杂志[J],2005,5(4):169-271
79.Metzler C,Fink C,LamPreeht P,et al.Maintenanee of remission with leflunomide in Wegener’s granulomatosis.Rheumatology(Oxford),2004,43(3):315-320
80.Ha H,Kim KH.Amelioration of diabetic microalbuinuria and lipid peroxidation by captopril.Yonsei Med J,1992,(33):217-273
81.Brien RC,PaPazoglou D,Allen T,et al.The effeets of perindopril versus triple therapy on albuminuria in normotensive diabetic rats.Kidney Int,1990,38:552-553
82.Marre M,Chatelier G,Lebiane N,et al.Prevention of diabetic nephopathy with enalapril in normotensive diabetes with mieroalbu-minuria.BMJ,1988,297:1092-1095
83.莫湛宇,梁东,司徒玉,等.黄芪对肾病综合征患者氧化应激影响的研究[J].中国中西医结合肾病杂志,2004,5(4):209
84.苗明三,方晓艳.怀地黄多糖免疫兴奋作用的实验研究[J].中国中医药科技,2002,(3):159
85.熊玉兰,王金华,屠国瑞,等.熟地黄麦角甾苷对小鼠肾毒血清肾炎治疗作用的研究.世界科学技术一中医药现代化,2006,8(5):46-48
86.徐强,王蓉,徐丽华,等.土茯苓对细胞兔疫和体液免疫的影响.中国免疫学杂志,1993,9(1):39
87.朱南山,李丽立,张彬.党参的生物学功能及其应用前景.饲料工业,2006,(27)20:57-58
88.田丽婷,马龙,堵年生.齐墩果酸的药理作用研究概况[J].中国中药杂志,2002,27(12):884
89.Zhang Yong-ciang,Xing-tian,Zho,Jin-huang.Effeets of L-ciumbar barum polysaeeharides and their combination with Corynebaeterium parvum on the tumoristaiic activity of peritoneal maerophages in mice[J].ChinaJphar Toxi,1989,3(3):169-174
90.董庆华,钟献,郑树.康莱特注射液对肺癌A549细胞环氧化酶作用的研究[J].中国中药杂志,2005,30(20):1621-1623
91.肖锦松,崔风军,宁廷选,等.玉竹、菟丝子醇提物对烧伤小鼠免疫功能的影响.中国中药杂志,1990,15(9):45-47
92.范美华,王健鑫,李鹏,等.益母草的研究进展[J].中国药物与临床,2006,6(7):528-529
93.徐勇,智光,郑思新.益母草的心血管药理作用及临床应用[J].世界急危重病医学杂志,2006,3(3):1312-1314
94.Frenk S.Experimental nephritie syndrome induced in rats by aminonueleoside.Proc Soe Exp Biol Med,1955,89:424-429
95.Sternberg SS,Philips FS.BIPhasic intoxieation and nephritic syndrome in rats given daunomycin.Proe Amer Assoe Caneer Res,1967,8:64-70
96.Bertani T,Poggi A,Pozzoni R,et al.Adriamycin induced ne-phrotic syndrome in rats.Lab Invest,1982,46:16-23
97.Newan David J,Pugia Miehael J,Lott John A,et al.Urinary protein and albunin excretion correted by creatinine and speeifiegravity[J].Clinica Chimica Aeta,2000,294(1-2):139-155
98.Hartmann A,Jenssen T,Midtvedt K,e tal.Protein-crearinine ratio-a simple method for proteinuria assessment in clinieal practiee[J].Tidsskrift for Den NorskeLaeggforening,2002,122(22):2180-2183
99.National Kidney Foundation.K/DOQI clinieal praetice guidelines for chronie kidney Disease:evaluation,clawwification and stratification[J].Am J Kidney Dis,2002,39(suppi):1-17
100.贺丹,柴华旗.黎曼.晨尿尿蛋白/尿肌酐比和24小时尿蛋白定量的临床评价.苏州大学学报(医学版).2004,24(6):861-863
101.梅长林等.血、尿β2-GM蛋白测定的临床意义及评价.中国实用内科杂志.[J],1999,19(4):200-202
102.Smoyer WE,Mundel P.Regulation of podoeyte scucture during the development of nephrotic syndrome.J Mbl Med,1998,76(3-4):172-183
103. Tryggvson K,Wartiovaara J.Molecular basis of glomerular permselectivity.Curr Opin Nephrol Hypertens.2001;10(4):543-9
2.Gansevoort R,de Zeeuw D,de Jong PE.Long-terin benefts of the antiproteinuric effect of ungiotensin-eonverting enzyme inhibition in nondiabetin renal diseases.AM J Kidney Dis,1993,22:202
3.Lewis EJ,Hunsicker L,Bain RP et al.For the Collaborative Study Group:The effect of angiotensin-converting-enayme inhibition on diabetic nephropathy.N Engl J Med,1993,329:1456
4.Jafar TH,Schnid CH,Landa M et al.Angiotensin-converting enzyme inhibition and progression of nondiabetic renal disease.A meta-analysis of patient-level data.Ann Intern Med,2001,135:73
5.仝小林,张志远.蛋白尿的中医治疗.中国医药学报[J],2002,17(2):115
6.刘伟,贝岩.中药辨证治疗蛋白尿探析.辽宁中医杂志[J],2005,32(3):225
7.郭立中,毛炜,刘玉宁,等.叶传惠教授对肾炎蛋白尿的病机认识及治疗经验.中国中西医结合肾病杂志[J],2001,2(3):128
8.李亦聪,冯天保.谢桂权教授治疗慢性肾炎蛋白尿经验介绍.新中医[J],2006,38(4):16
9.沈庆法.肾脏病蛋白尿的中医论治.中国临床医生[J],2004,32(8):50
10.金劲松.邵朝弟教授治疗蛋白尿的经验.中国中西医结合肾病杂志[J],2006,7(9):501
11.张琼.黄淑芬从络病论治肾性蛋白尿.中医杂志[J],2004,46(10):745
12.邓聪.从风郁瘀论治蛋白尿.中华中医药杂志[J],2006,21(8):506
13.沈庆法.清利法治疗蛋白尿.上海中医药杂志[J],2006,40(2):23
14.袁红霞,林嫦娥.黄文政教授治疗顽固性蛋白尿经验总结.天津中医药[J],2003,20(5):18-19
15.刘宏伟,王国栋,张国强.国医匠时振声教授学术贡献撷萃.中医药学刊[J],2001,19(6):534
16.杜秋霞.叶传惠教授诊治肾性蛋白尿经验.四川中医[J],2001,19(5):4
17.黄臻,邹嘉玉.皮持衡治疗单纯肾性蛋白尿的经验.江西中医药[J],2006,(37)284:6
18.陈瑜.中医辨治小儿慢性肾炎蛋白尿七法.中医研究[J],2001(14)5:30-31
19.庞莉.刘莉.周保林.贺永清主任医师治疗蛋白尿的经验.现代中医药[J],2005,3:22-23
20.邹玺,熊宁宁.长期应用清热利湿和络法对慢性肾炎患者蛋白尿变化的影响.中医杂志[J], 2004,45(4):266-269
21.方志传.养脾为主治疗慢性肾炎蛋白尿.湖北中医杂志[J],2001,23(8):346
22.张丽霞.升阳益气固肾化痪治疗慢性肾炎蛋白尿疗效观察.中医药学刊[J],2006,24(5):965-966
23.李玉花.活血化瘀法在蛋白尿治疗中的运用.实用中西医结合临床[J],2005,(5)2:55-56
24.王静.补肾固涩法为主治疗蛋白尿30例.陕西中医[J],2001,22(10):590
25.陈志强方敬刘丽等.青藤碱对系膜增生性肾小球肾炎影响的实验研究[J].中国老年学杂志,2007,27:27-28
26.刘志红,戴春笋,李恒等.雷公藤内酷醇对人近端肾小管上皮细胞单核细胞趋化因子合成的影响.肾脏病与透析肾移植杂志[J],2000,9(5):431-435
27.张万祥,秦建国,张荣等.参蔑益肾汤治疗疗肾性蛋白尿45例观察.时珍国医国药,2007,18(6):1482-1483
28.韩进庭.自拟消蛋白饮联合西药治疗蛋白尿30例.长春中医药大学学报,2007,23(4):59
29.刘永琴,刘淮阳.成人无症状性血尿蛋白尿的临床病理分析及预.四川医学[J],2002,23(1),32
30.尹莲芳,淮家伉,弓玉祥等.黄蜀葵花对阿霉素肾病大鼠钠储留改善作用的机制.中华肾脏病杂志[J].1999,15(5):324-325
31.杨俊伟,戴春笋,陈朝红等.雷公藤内酷醇对T细胞功能的影响与cAMP/PKA的关系.肾脏病与透析肾移植杂志[J],1998,7(2):106-112
32.黄黎明,梁恒,邢建宇等.山茱英提取物对慢性肾炎小鼠的药理作用及蛋白质组学效应的实验研究.中国药理学通报[J],2004,20(10):1144-1150
33.李宏伟,王荣欣.升阳益胃汤治疗慢性肾病蛋白尿42例.中国中医药科技,2001,8(3):161
34.吴金国,陈志龙,张黎明.急慢性肾炎中药治疗研究进展.中医药信息[J],2001,18(4):5
35.齐占华.益肾液治疗肾小球性蛋白尿疗效分析.实用中医药杂志[J],2005,21(10):585
36.梁汝钊.毛文忠.刘吉样.益肾煎治疗肾小球性蛋白尿31例.陕西中医[J],2005,26(8):753-754
37.练建红.刘恩棋.蒙向欣等.益肾I方治疗肾小球性蛋白尿的临床研究.福建中医药[J],2007,3(3):1-3
38.雷作熹,罗仁,董晓蕾等.小四五颗粒对糖尿病大鼠肾保护作用研究[J].中药新药与临床药理[J],2003,14(2):93-96
39.代方国,魏敏,孙晓敏等.小四五颗粒治疗慢性肾病蛋白尿30例临床观察[J].新中医,2007,39(8):33-34
40.何岚,王宁生.五苓散减轻阿霉素肾病大鼠蛋白尿的实验研究.中成药[J],2006,28(10):1532-1534
41.赵飞,王晓霞,程广清等.疏血通注射液治疗肾性蛋白尿69例临床观察[J].山东中医药大学学报,2007,31(4):294-295
42.Mundel P,Shankland SJ.Podocyte biology and resPonse toinjury.J Am Soe Neplirol,2002,13(12):3005-3015
43.Dustin ML,Olszowy MW,Holdorf AD,et al.A novella daptor protein or chestrates receptor Patterning and cytoskeletal polarity in T-cell contaets.Cell,1998,94(5):667-677
44.Shih NY,Li J,Karpitskii V,et al.Congenital nephritic syndrome in mice lacking CD2-assoeiated protein. Seienee,1999,286(5438):312-315
45.Pavenstadt H,Kriz W,Kretzler M.Cell biology of the glomerular podoeyte.Physiol Rev,2003,83(1):253-307
46.Coward RJ,Foster RR,Patton D,et al.Nephrotic plasma alters slit diaphragm dependent signaling and translocates nephrin,Podoein,and CD2 assoeiated protein in cultured human podoeytes.J Am Soc Nephrol,2005,16(3):629-637
47.Huber TB,Hardeben B,Kim J,et al.Nephrin and CD2AP associate with Phosphoinositide 3-OH kinase and stimulate AKT-dependent signaiing[J].MolCel lBiol,2003,23(14):4917-4928
48.Cantley LC.The phosphoinositide3-kinase pathway[J].Seienee,2002,296(5573):1655-1657
49. Wartiovaara J,Ofverstedt LG,Khoshnoodi J,et a1.Nephrin strands contribute to a porous slit diaphragm scafold as revealed by electron tomography.J Clin Invest,2004,114:1475-1483.
50.Beltcheva O,Martin P,Lenkkeri U,et a1.Mutation spectrum in the nephrin gene(NPHS1)in congenital nephritic syndrome.Hum Mutation,2001,17:368-373.
51.Verma R,Kovari I,Soofi A,et a1.Nephrin ectodomain engagement results in Src kinase activation,nephrin phosphorylation,Nek recruitment,and actin polymerization.J ClinInvest,2006,116:1346-1359.
52.Lahdenpera J , Kilpelainen P,Liu XL,et a1.Clustering-induced tymsine phosphorylation of nephrin by Src family kinases.Kidney Int,2003,64:404-413.
53.Kaplan JM,Kim SH,North KN, e tal.Mutations in ACTN4,encoding alpha-aetinin-4,cause familial foeal segmental glomerulaselerosis[J].Nat Genet,2000,24:251-256
54.Yao J,Le TC,Kos CH,et al.AIPha-actinin-4- mediated FSGS:an inherited kidney disease caused by an aggre-gated and rapidly degraded cytaskeletal protein[J] Plos Biol,2004,2(6):787-794
55.Weins A,Kenlan P,Herbert S,et al.Mutational and Bio-logieal Analysis of alpha-actinin-4 in focal segmental glomeruloselerosis[J].J Am Soe Nephrol.2005,16(12):3694-3701
56.何伟春,邢昌赢,孙彬等.CD2AP和α-actinin-4在大鼠阿霉素肾病模型中的表达.南京医科大学学报(自然科学版),2006,26(11):1005-1007
57.Boute N.Gribouval O.Roselli S.et al.NPHS2.encoding the gomerular protein Podoein,is mutated in autosomal recessive steroid- resistant nephritic syndrome.Nat Genet2000,24:349-354
58.Sehwarz K.Simons M.Keiser,J.et al.Podoein,araft-assoeiated component of the gomemlar slit diaphragm,interacts with CD2AP and nephrin.J Clin Invest,2001,108(11):1621-1629
59.Eiser J,Kriz W.The golmerular slit diaphragm is a modified adherens juntiln[J].J Am Sco Nephrol,2000,11(1):1
60.叶任高,沈清瑞.肾脏病诊断与治疗学.北京:北京人民卫生出版社[M],1994:208
61.叶任高,刘冠贤.临床肾脏病学.北京:北京人民卫生出版社[M],1997:52-53
62.林善琐,陈靖.肾小球疾病治疗最新进展.中国实用内科杂志,2000,20:26-29
63.Edited by Barry M.Brenner The kidneyy[J] .Science press sixth dition,2000,1271-1277
64.Albert Matalon,Anthong Valeri,and Grerald B Appel:Treatment of Focal segmental Glomerulosclerosis[J] .Seminars in Nephrology.2000,20:309-317
65.何敏华,叶任高,马翅云.糖皮质激素在肾小球疾病治疗中的进展.大理学院学报[J],2003,(2)3:52
66.李幼姬,叶任高,姜搅.成人原发性肾病综合征治疗的探索.中华肾脏病杂志[J],1995,11(3):133-136
67.黎磊石,张训,陈光永,等.雷公藤治疗肾小球肾炎的临床研究.中华内科杂志[J],1981,20(4):216
68.黎磊石,刘志红.雷公藤在肾脏病领域应用的前景.肾脏病与透析肾移植杂志[J],1997,6(3):203
69.施向东,范德墉,陆玉良.雷公藤多贰片对肾性蛋白尿的作用.中国中西医结合肾病杂志[J],2000,1(4),224-225
70.朱汉威,朱淳,陆玮,等.雷公藤多试长程治疗肾小球肾炎疗效观察.上海第二医科大学学报[J],2002,22(6):543-544
71.冯为盛,姜继元.霉酚酸酷治疗难治性肾病综合征.中华肾脏病杂志[J],1999,15(5):287
72.黄茂芹,周森,陈裕盛.霉酚酸酷治疗肾病综合征8例观察.中华肾脏病杂志[J],2000,16(6):386
73.刘光陵,高远斌,夏正坤,等.霉酚酸酷在小儿肾小球疾病治疗中的应用效果.中华儿科杂志[J],1999,37(10):640
74.沈平雁,蒋颈松.霉酚酸醋在治疗肾小球疾病中的应用.实用医学杂志[J],1999,15(9):731
75.Lou T,Wang C,Chen Z,et al.Randomised controlled trial of eflunomide in the treatment of immunoglobulin A nephropathy.Nephrology(Carlton),2006,11(2):113-116
76.王成,娄探奇,唐哗等.来氟米特治疗难治性肾病综合征60例临床研究.中国实用内科杂志[J],2005,25(12):1096-1095
77.崔太根,侯凡凡,倪兆慧,等.来氟米特联合糖皮质激素治疗增殖型狼疮性肾炎的多中心对照临床试验研究.中华内科杂志[J],2005,44(9):672-676
78.任岳钦,李延国,马云航.来氟米特治疗过敏性紫瘫性肾炎的临床研究.临床肾脏病杂志[J],2005,5(4):169-271
79.Metzler C,Fink C,LamPreeht P,et al.Maintenanee of remission with leflunomide in Wegener’s granulomatosis.Rheumatology(Oxford),2004,43(3):315-320
80.Ha H,Kim KH.Amelioration of diabetic microalbuinuria and lipid peroxidation by captopril.Yonsei Med J,1992,(33):217-273
81.Brien RC,PaPazoglou D,Allen T,et al.The effeets of perindopril versus triple therapy on albuminuria in normotensive diabetic rats.Kidney Int,1990,38:552-553
82.Marre M,Chatelier G,Lebiane N,et al.Prevention of diabetic nephopathy with enalapril in normotensive diabetes with mieroalbu-minuria.BMJ,1988,297:1092-1095
83.莫湛宇,梁东,司徒玉,等.黄芪对肾病综合征患者氧化应激影响的研究[J].中国中西医结合肾病杂志,2004,5(4):209
84.苗明三,方晓艳.怀地黄多糖免疫兴奋作用的实验研究[J].中国中医药科技,2002,(3):159
85.熊玉兰,王金华,屠国瑞,等.熟地黄麦角甾苷对小鼠肾毒血清肾炎治疗作用的研究.世界科学技术一中医药现代化,2006,8(5):46-48
86.徐强,王蓉,徐丽华,等.土茯苓对细胞兔疫和体液免疫的影响.中国免疫学杂志,1993,9(1):39
87.朱南山,李丽立,张彬.党参的生物学功能及其应用前景.饲料工业,2006,(27)20:57-58
88.田丽婷,马龙,堵年生.齐墩果酸的药理作用研究概况[J].中国中药杂志,2002,27(12):884
89.Zhang Yong-ciang,Xing-tian,Zho,Jin-huang.Effeets of L-ciumbar barum polysaeeharides and their combination with Corynebaeterium parvum on the tumoristaiic activity of peritoneal maerophages in mice[J].ChinaJphar Toxi,1989,3(3):169-174
90.董庆华,钟献,郑树.康莱特注射液对肺癌A549细胞环氧化酶作用的研究[J].中国中药杂志,2005,30(20):1621-1623
91.肖锦松,崔风军,宁廷选,等.玉竹、菟丝子醇提物对烧伤小鼠免疫功能的影响.中国中药杂志,1990,15(9):45-47
92.范美华,王健鑫,李鹏,等.益母草的研究进展[J].中国药物与临床,2006,6(7):528-529
93.徐勇,智光,郑思新.益母草的心血管药理作用及临床应用[J].世界急危重病医学杂志,2006,3(3):1312-1314
94.Frenk S.Experimental nephritie syndrome induced in rats by aminonueleoside.Proc Soe Exp Biol Med,1955,89:424-429
95.Sternberg SS,Philips FS.BIPhasic intoxieation and nephritic syndrome in rats given daunomycin.Proe Amer Assoe Caneer Res,1967,8:64-70
96.Bertani T,Poggi A,Pozzoni R,et al.Adriamycin induced ne-phrotic syndrome in rats.Lab Invest,1982,46:16-23
97.Newan David J,Pugia Miehael J,Lott John A,et al.Urinary protein and albunin excretion correted by creatinine and speeifiegravity[J].Clinica Chimica Aeta,2000,294(1-2):139-155
98.Hartmann A,Jenssen T,Midtvedt K,e tal.Protein-crearinine ratio-a simple method for proteinuria assessment in clinieal practiee[J].Tidsskrift for Den NorskeLaeggforening,2002,122(22):2180-2183
99.National Kidney Foundation.K/DOQI clinieal praetice guidelines for chronie kidney Disease:evaluation,clawwification and stratification[J].Am J Kidney Dis,2002,39(suppi):1-17
100.贺丹,柴华旗.黎曼.晨尿尿蛋白/尿肌酐比和24小时尿蛋白定量的临床评价.苏州大学学报(医学版).2004,24(6):861-863
101.梅长林等.血、尿β2-GM蛋白测定的临床意义及评价.中国实用内科杂志.[J],1999,19(4):200-202
102.Smoyer WE,Mundel P.Regulation of podoeyte scucture during the development of nephrotic syndrome.J Mbl Med,1998,76(3-4):172-183
103. Tryggvson K,Wartiovaara J.Molecular basis of glomerular permselectivity.Curr Opin Nephrol Hypertens.2001;10(4):543-9