Your Position: Home > Journal List > China Medicine > Paper

The research of adriamycin induced focal segmental glomerulosclerosis in rat

( views:265, downloads:0 )
Author:
WANG Chen-dan(Department of Nephrology, the Second Hospital of Shanxi Medical University,Taiyuan 030001, China)
LI Rong-shan(Department of Nephrology, the Second Hospital of Shanxi Medical University,Taiyuan 030001, China)
QIAO Xi(Department of Nephrology, the Second Hospital of Shanxi Medical University,Taiyuan 030001, China)
WANG Chen(Department of Nephrology, the Second Hospital of Shanxi Medical University,Taiyuan 030001, China)
Journal Title:
China Medicine
Issue:
Volume 06, Issue 12, 2011
DOI:
10.3760/cma.j.issn.1673-4777.2011.12.004
Key Word:
Adriamycin-induced nephropathy;Rat;Focal segmental giomeruloeclerosis

Abstract: Objective To establish the model of rat adriamycin induced nephritis (AIN)similar to the human renal glomerular disease in patho and amynology.Methods Forty Sprague Dawley rats were randomly divided into model(32) and control group (8).They were randomly divided into the first injection of adriamycin after 2 weeks,4 weeks,8 weeks and 12 weeks.Rat tail of model group vein were injected of adriamycin for two times;control group was given two injections of the same amount of normal saline through the tail veins of rats according to the method with the model group.The level of 24 hour urinary protein,serum total protein(TP),albumin(ALB),cholesterin (CH),triglyeride ( TG),serum urea nitrogen (BUN) and serum creatinine ( Cr ) were measured.The renal pathological changes were observed by light microscope and electron microscope.The expression of fibronectin(FN)and laminin (LN)was analyzed by immunohistochemistry.Matrix metalloproteinases(MMP)-2,MMP-9 and transforming grouth factor(TGF)-β1 were detected by enzyme linked immunosorbent assay.Results Compared with control group,the level of 24 hour urinary protein in AIN model at 2th,4th,8th and 12th week increased( P < 0.01 ),TP and ALB were obviously decreased[ (50.7 ± 3.6),(42.2 ± 3.4),(40.4 ± 3.1 ),(41.7 ± 3.3 ) g/L vs (62.8 ±2.8)g/L;(22.2 ±1.8),(16.4 ±1.7),(14.8 ±2.1),(13.0 ±2.2)g/L vs (29.0 ± 1.3)g/L]; TG and CH in AIN model group were obviously increased [ (5.2 ± 1.4),(6.1 ± 1.5 ),(7.3 ± 1.5 ),(7.2 ± 1.2 ) mmol/L vs (0.6 ±0.3)mmol/L;(3.8 ±1.7),(5.6 ±1.9),(8.6 ±2.7),(9.6 ±1.6)mmol/L vs (1.3 ±0.1)mmol/L] ;focal segmental glomerulosclerosis( FSGS)were observed in 12th week group; The level of TGF-β1 in serum were obviously increased,the level of MMP-2 and M MP-9 reduced [ ( 151.4 ± 2.4 ),( 100.5 ± 3.1 ),(76.5 ± 3.6),( 83.7 ±3.1 ) μg/L; (73.4 ± 2.7),(58.9 ± 2.2 ),( 35.4 ± 2.0),( 33.3 ± 1.5 ) μg/L ] ; the expression and distribution of FN,LN increased significantly.Conclusion After the first large doses of adriamycin (6 mg/kg)shockb is induced,plus one week after low dose (4 mg/kg) administration in rats,the rats appear visiblely part of giomerular appearance of FSGS at the end of 12 weeks.

  • [1]Li LS,Liu ZH.Epidemiologic data of renal diseases from a single unit in China:analysis based on 13,519 renal biopsies.Kidney Int,2004,66(3):920-923.
  • [2]Pedrycz A,Wieczorski M,Czemy K.Features of proteinuria in rat kidney in experimental nephrotic syndrome.Ann Univ Mariae Curie Sklodowska Med,2000,55:275-279.
  • [3]王泰华,钱家麒,张介玉,等.阿霉素肾病肾硬化动物模型的实验改进.肾脏病与透析肾移植杂志,1997,6(2):191-193.
  • [4]张浩,季龙振,伍锟,等.弥漫性系膜增生伴局灶节段性肾小球硬化大鼠模型的建立.中国医师杂志,2002,4(8):843.
  • [5]郑东辉,邢昌赢,陈菊花.霉酚酸酯对局灶节段性肾小球硬化(FSGS)治疗作用的研究.医学理论与实践,2006,11 (19):1251-1254.
  • [6]朱吉莉,贾汝汉,王学玉.依贝沙坦对阿霉素肾病大鼠肾小管间质的保护作用.中华肾脏病杂志,2003,19(1):53.
  • [7]Kriz W,LeHir M.Pathways to nephron loss starting from glomerular diseases-insights from snimal models.Kidney Int,2005,67(2):404-419.
  • [8]Pollak MR.The genetic basis of FSGS and steroid-resistant nephrosis.Semin Nephrol,2003,23(2):141-146.
  • [9]Petermann AT,Hiromura K,Blonski M,et al.Mechanical stress reduces podocyte proliferation in vitro.Kidney Int,2002,61 (1):40-50.
  • [10]Shankiand SJ.The podocyte's response to injury:role in proteinuria and glomerulosclerosis.Kidney Int,2006,69(12):2131-2147.
  • [11]Neilson EG.Mechanisms of disease:Fibroblasts--a new look at an old problem.Nat Clin Pract Nephrol,2006,2(2):101-108.
  • [12]Asanuma K,Yanagida-Asanuma E,Takagi M,et al.The role of podocytes in proteinuria.Nephrology (Carlton),2007,12 Suppl 3:S15-S20.
  • [13]Liu Y.Renal fibrosis:new insights into the pathogenesis and therapeutics.Kidney Int,2006,69(2):213-217.
  • [14]Fan JM,Ng YY,Hill PA,et al.Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro.Kidney Int,1999,56(4):1455-1467.
  • [15]Fukasawa H,Yamamoto T,Suzuki H,et al.Treatment with anti-TGF- beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling.Kidney Int,2004,65 (1):63-74.
  • [16]Goumenos DS,Kalliakmani P,Tsakas S,et al.Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment,in patients with crescentic nephritis.BMC Nephrol,2005,6:16.
  • [17]Moussad EE,Brigstock DR.Connective tissue growth factor:what's in a name? Mol Genet Metab,2000,71 (1-2):276-292.
  • [18]Yang J,Liu Y.Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis.J Am Soc Nephrol,2002,13(1):96-107.
  • [19]Fan JM,Huang XR,Ng YY,et al.Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-betal-dependent mechanism in vitro.Am J Kidney Dis,2001,37(4):820-831.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn