期刊文献+

慢性移植性肾病大鼠尿液中结缔组织生长因子的检测价值 被引量:1

Urinary connective tissue growth factor as a biomarker chronic allograft nephropathy in a rat model
原文传递
导出
摘要 目的探讨尿液中结缔组织生长因子(CTGF)成为慢性移植性肾病(CAN)的分子标记的可能性。方法改良Kamada法建立雄性F344→Lewis大鼠原位同种异体CAN模型,同时设定假手术组作为对照。分别测定移植后4、8、12和16周的血清肌酐和移植肾的Banff评分;Western印迹测定移植肾CTGF的表达变化;间接酶联免疫吸附试验测定血液和尿液中CTGF的表达变化;每个时间点,模型组6只大鼠,假手术组3只大鼠。对尿CTGF变化与CAN的进程进行相关性分析。结果4、8、12和16周模型组大鼠血清肌酐和移植肾的Banff评分逐渐升高,具有时间依赖性。模型组移植后肾组织中CTGF蛋白表达在术后4、8、12、16周分别为0.55±0.02、0.80±0.03、0.90±0.03和1.14±0.11,均明显高于假手术组(0.33±0.05,均P〈0.01)。模型组尿液和血清中CTGF表达从术后4周开始出现,高水平的表达保持到术后16周;尿液中CTGF在术后4、8、12和16周分别是(2.9±0.7)、(12.9±3.6)、(32.3±11.4)和(31.0±8.9)ng/mg肌酐,均明显高于假手术组[(0.7±0.3)ng/mg肌酐,均P〈0.01]。尿CTGF与血清肌酐(r=0.848)、Banff评分(r=0.874)和移植。肾中CTGF表达(r=0.747)均具有明显的相关性(均P〈0.01)。结论CTGF在CAN的的进程中可能扮演了重要角色,尿CTGF可以成为CAN的分子标记。 Objective To determine whether urinary connective tissue growth factor (CTGF) can be a molecular marker for chronic allograft nephropathy (CAN) in a rat model. Methods F344 rat renal grafts were orthotopically transplanted into Lewis rats (n = 24 ) . Lewis rats underwent sham operation as control group(n = 12). Kidney grafts were harvested at Weeks 4, 8, 12 and 16 respectively. Serum creatinine (SCr) was measured. The CAN grades were evaluated according to the Banff 97 schema The expressions of CTGF in kidney, serum and urine were determined by Western blot and competitive indireet ELISA. Spearman correlation analysis was used to compare CTGF expression and the development of CAN. Results The expression of CTGF in the graft group was markedly elevated in comparison with the control group. Statistics analysis of CTGF protein in kidney detected by Western blot showed significant differences between these five groups ( 0. 33 ± 0. 05 for control, 0. 55 ±0. 02 for Week 4, 0. 80 ± 0. 03 for Week 8, 0. 90 ±0. 03 for Week 12 and 1.14±0. 11 for Week 16, P 〈0. 01). Both urine and serum CTGF increased by Week 4 and maintained a high level up to Week 16. The urinary CTGF of renal allografts was (2. 9 ±0.7), (12.9±3.6), (32.3±11.4) and (31.0±8.9) ng/mg creatinine for Weeks 4, 8, 12 and 16 respectively. The urinary levels were positively correlated with SCr, Banff scores and expression of CTGF in the graft kidney( r =0. 848,0. 874,0. 747, all P 〈 0.01 ). Conclusions CTGF plays a significant role in the pathological changes of CAN after kidney transplantation. Urinary CTGF has the potential as a biomarker for predicating the clinical course of CAN.
出处 《中华医学杂志》 CAS CSCD 北大核心 2010年第28期1999-2003,共5页 National Medical Journal of China
基金 贵州省科技厅基金[黔科合J字(2009)2318号] 贵州省特助基金(TZJF-2009-11)
关键词 肾移植 尿 结缔组织生长因子 慢性移植性肾病 Kidney transplantation Urine Connective tissue growth factor Chronic allograft nephropathy
  • 相关文献

参考文献10

  • 1Schwarz A,Mengel M,Gwinner W,et al.Risk factors for chronic allograft nephropathy after renal transplantation:a protocol biopsy study.Kidney Int,2005,67:341-348.
  • 2Cheng O,Thuillier R,Sampson E,et al.Connective tissue growth factor is a biomarker and mediator of kidney allngraft fibrosis.Am J Transplant,2006,6:2292-2306.
  • 3Luo GH,Lu YP,Song J,et al.Inhibition of connective tissue growth factor by small interfering RNA prevents renal fibrosis in rats undergoing chronic allograft nephropathy.Transplant Proc,2008,40:2365-2369.
  • 4Kamada N.A description of cuff techniques for renal transplantation in the rat.Use in studies of tolerance induction during combined liver grafting.Transplantation,1985,39:93-95.
  • 5Racusen LC,Solez K,Colvin RB,et al.The Banff 97 working classification of renal allngraft pathology.Kidney Int,1999,55:713-723.
  • 6Nankivell BJ,Chapman JR.Chronic allograft nephropathy:current concepts and future directions.Transplantation,2006,81:643-654.
  • 7杨敏,黄海长,李惊子,王海燕.结缔组织生长因子协同转化生长因子β_1的促肾纤维化效应[J].中华医学杂志,2004,84(7):569-573. 被引量:34
  • 8Thomson SE,McLennan SV,Kirwan PD,et al.Renal connective tissue growth factor correlates with glomerular basement membrane thickness and prospective aibuminuria in a non-human primate model of diabetes:possible predictive marker for incipient diabetic nephropathy.J Diabetes Complications,2008,22:284-294.
  • 9Li G,Xie Q,Shi Y.Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats.J Gene Med,2006,8:889-900.
  • 10张春,朱忠华,刘建社,杨晓,邓安国.结缔组织生长因子对肾小管上皮细胞转分化的调节机制[J].中华医学杂志,2005,85(41):2920-2925. 被引量:22

二级参考文献18

  • 1Florquin S, Rouschop KM. Reciprocal functions of hepatocyte growth factor and transforming growth factor-betal in the progression of renal diseases: a role for CD447 Kidney Int, 2003, (Suppl) : s15-20.
  • 2Zeisberg M, Bonner G, Maeshima Y, et ak Renal fibrosis : collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation. Am J Pathol, 2001, 159: 1313-1321.
  • 3Yokoi H, Mukoyama M, Sugawara A, et al. Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis.Am J Physiol Renal Physiol, 2002, 282 : F933-942.
  • 4Gore-Hyer E, Shegogu-e D, Markiewicz M, et aL TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol, 2002, 283: F707-F716.
  • 5Yokoi H, Sugawara A, Mukoyama M, et aL Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: a potential target for preventing renal fibrosis. Am J Kidney Dis, 2001, 38: s134-s138.
  • 6Frazier KS, Paredes A, Dube P, et aL Connective tissue growth factor expression in the rat remnant kidney model and association with tubular epithelial cells undergoing transdifferentiation. Vet Pathol,2000, 37: 328-335.
  • 7Border WA,Noble NA.Transforming growth factor beta in tissue fibrosis.N EW,1 J Med,1994,331:1286-1292.
  • 8Ito Y, Aten J, Bende RJ, et al. Expression of connective tissue growth factor in human renal fibrosis. Kidney Int, 1998, 53: 853- 861.
  • 9Zeisberg M, Kalluri IL The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med, 2004, 82: 175-181.
  • 10Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates tubular epithelial-myoflbroblast transdifferentiation in vitro.Kidney Int. 1999. 56: 1455-1467.

共引文献53

同被引文献36

  • 1Bestard O,Cruzado J M,la Franquesa M,GrinyóJ M.Biomarkers inrenal transplantation[J].Curr Opin Organ Transplant,2010,15:467-473.
  • 2Kurian S M,Heilman R,Mondala T S,Nakorchevsky A,Hewel J A,Campbell D,et al.Biomarkers for early and late stage chronic al -lograft nephropathy by proteogenomic profiling of peripheral blood[J].PLoS One,2009,4:e6212.
  • 3Scherer A,Gwinner W,Mengel M,Kirsch T,Raulf F,SzustakowskiJ D,et al.Transcriptome changes in renal allograft protocol biopsiesat 3 months precede the onset of interstitial fibrosis/tubular atrophy(IF/TA)at 6 months[J].Nephrol Dial Transplant,2009,24:2567-2575.
  • 4Bodonyi-Kovacs G,Putheti P,Marino M,Avihingsanon Y,UknisM E,Monaco A P,et al.Gene expression profiling of the donor kid- ney at the time of transplantation predicts clinical outcomes 2 yearsafter transplantation[J].Hum Immunol,2010,71:451-455.
  • 5Koop K,Bakker R C,Eikmans M,Baelde H J,de Heer E,Paul LC,et al.Differentiation between chronic rejection and chronic cy- closporine toxicity by analysis of renal cortical mRNA[J].KidneyInt,2004,66:2038-2046.
  • 6Baón-Maneus E,Diekmann F,Carrascal M,Quintana L F,Moya-Rull D,Bescós M,et al.Two-dimensional difference gel electro- phoresis urinary proteomic profile in the search of nonimmune chro-nic allograft dysfunction biomarkers [J].Transplantation,2010,89:548-558.
  • 7Quintana L F,Campistol J M,Alcolea M P,Baón-Maneus E,Sol-González A,Cutillas P R.Application of label-free quantitativepeptidomics for the identification of urinary biomarkers of kidneychronic allograft dysfunction[J].Mol Cell Proteomics,2009,8:1658-1673.
  • 8Hu H,Aizenstein B D,Puchalski A,Burmania J A,Hamawy M M,Knechtle S J.Elevation of CXCR3-binding chemokines in urineindicates acute renal-allograft dysfunction[J].Am J Transplant,2004,4:432-437.
  • 9Hu H,Kwun J,Aizenstein B D,Knechtle S J.Noninvasive detectionof acute and chronic injuries in human renal transplant by elevationof multiple cytokines/chemokines in urine[J].Transplantation,2009,87:1814-1820.
  • 10Zhao D X,Hu Y,Miller G G,Luster A D,Mitchell R N,Libby P.Dif-ferential expression of the IFN-gamma-inducible CXCR3-bind- ing chemokines,IFN-inducible protein 10,monokine induced byIFN,and IFN-inducible T cell alpha chemoattractant in human car- diac allografts:association with cardiac allograft vasculopathy and a-cute rejection[J].J Immunol,2002,169:1556-1560.

引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部