血清中Ⅲ型胶原变化与梗阻性肾病肾纤维化关系的临床研究
|
摘要
目的：
探讨梗阻性肾病患者血清中Ⅲ型前胶原(Procollagen TypeⅢ, PCⅢ)及Ⅲ型前胶原氨基末端肽(Amino Terminal Peptide of ProcollagenⅢ, PⅢNP)浓度的变化与肾组织纤维化的相关性。由此筛选出能及早预测肾积水肾脏纤维化程度的具有临床意义的实验室指标,以求对肾积水的治疗有所指导。
方法：
本院泌尿外科收治肾积水患者30例,分为3组,肾脏轻度积水组、中度积水组、重度积水组各10例,另外取10例肾透明细胞癌(术后经病理证实)及肾外伤患者作为对照组；采用放射免疫法测定各组患者血清中PCⅢ及PⅢNP含量；三组肾积水患者各留取肾组织标本5例,对照组留取正常肾组织标本5例(肾透明细胞癌根治术患者取癌旁5cm以外的肾组织),标本行免疫组化SP法染色测定Ⅲ型胶原含量,HE染色测定肾小管肾间质病变程度,对血清中PCⅢ及PⅢNP含量与肾小管肾间质病变比率行相关性分析。
结果：
①三组肾积水患者血清中PCⅢ及PⅢNP值较对照组均升高,且随积水程度加重血清中PCⅢ及PⅢNP值逐渐升高,各组间比较有统计学意义(P<0.05)。
②各组肾积水患者肾小管、肾间质病变比率较对照组差异有统计学意义(P<0.05),且随积水程度加重,肾小管、肾间质病变比率增加。
③血清PCⅢ及PⅢNP浓度与病变肾小管、肾间质比率呈正相关(r=0.749,P<0.05)。
结论：
肾积水患者血清中PCⅢ及PⅢNP值较对照组明显升高,且随积水程度加重血清中PCⅢ及PⅢNP值逐渐升高；肾积水患者血清PCⅢ及PⅢNP值与肾脏肾小管、肾间质病变比率呈正相关,表明血清PCⅢ及PⅢNP与肾积水时肾间质病变纤维化密切相关。因此,在排除肾外脏器纤维化的前提下,推测血清PCⅢ及PⅢNP对早期判断肾积水肾脏纤维化进程具有一定意义。
Objective
This study was to explore the relevance of the changing of collagen typeⅢin serum of obstructive nephropathy and renal fibrosis, then we could elucidate the diagnosis value of serum PCⅢand PⅢNP concentration on the renal fibrosis.
Methods
Thirty patients with hydronephrosis fibrosis were separated to three group:the group of Mild renal fibrosis, Moderate renal fibrosis and Severe renal fibrosis group. Also take 10 cases of renal trauma in patients with renal cell carcinoma as the control group. The serum of each patient was reserved before operation. Collagen typeⅢwas measured by immunohistochemical staining and PCⅢand PⅢNP were measured by radioimmunoassay (RIA). The five renal tissue specimens of each patient were taken out to measure the tubular interstitial lesions by HE staining and to measure the collagenⅢcontents by immunohistochemical SP staining. We analyzed the correlation between the tubular interstitial lesions and the PCⅢand PⅢNP in the serum.
Results
①. PCⅢand PⅢNP in serum of three groups of renal fibrosis in patients with hydronephrosis were higher than the control group, and the value of the PCⅢand PⅢNP in the serum increased gradually with the increasing degree of hydronephrosisi.
②. Interstitial fibrosis in kidneys of patients of hydronephrosis was observed more pronounced than the control groups,and the rate of the tubular interstitial lesions increased gradually with the increasing degree of hydronephrosisi.
③. PCⅢand PⅢNP in serum were positively correlated with the the tubular interstitial lesions.
Conclusions:
①.PCⅢand PⅢNP in serum of three groups of renal fibrosis in patients with hydronephrosis are higher than the control group,and the value of the PCⅢand PⅢNP in the serum increased gradually with the increasing degree of hydronephrosisi. The PCⅢand PⅢNP in serum are correlative with renal interstitial fibrosis in hydronephrosis. PCⅢand PⅢNP in serum can be used to indicate renal fibrosis in hydronephrosis on condition that other organ fibrosis could be excluded.
探讨梗阻性肾病患者血清中Ⅲ型前胶原(Procollagen TypeⅢ, PCⅢ)及Ⅲ型前胶原氨基末端肽(Amino Terminal Peptide of ProcollagenⅢ, PⅢNP)浓度的变化与肾组织纤维化的相关性。由此筛选出能及早预测肾积水肾脏纤维化程度的具有临床意义的实验室指标,以求对肾积水的治疗有所指导。
方法：
本院泌尿外科收治肾积水患者30例,分为3组,肾脏轻度积水组、中度积水组、重度积水组各10例,另外取10例肾透明细胞癌(术后经病理证实)及肾外伤患者作为对照组；采用放射免疫法测定各组患者血清中PCⅢ及PⅢNP含量；三组肾积水患者各留取肾组织标本5例,对照组留取正常肾组织标本5例(肾透明细胞癌根治术患者取癌旁5cm以外的肾组织),标本行免疫组化SP法染色测定Ⅲ型胶原含量,HE染色测定肾小管肾间质病变程度,对血清中PCⅢ及PⅢNP含量与肾小管肾间质病变比率行相关性分析。
结果：
①三组肾积水患者血清中PCⅢ及PⅢNP值较对照组均升高,且随积水程度加重血清中PCⅢ及PⅢNP值逐渐升高,各组间比较有统计学意义(P<0.05)。
②各组肾积水患者肾小管、肾间质病变比率较对照组差异有统计学意义(P<0.05),且随积水程度加重,肾小管、肾间质病变比率增加。
③血清PCⅢ及PⅢNP浓度与病变肾小管、肾间质比率呈正相关(r=0.749,P<0.05)。
结论：
肾积水患者血清中PCⅢ及PⅢNP值较对照组明显升高,且随积水程度加重血清中PCⅢ及PⅢNP值逐渐升高；肾积水患者血清PCⅢ及PⅢNP值与肾脏肾小管、肾间质病变比率呈正相关,表明血清PCⅢ及PⅢNP与肾积水时肾间质病变纤维化密切相关。因此,在排除肾外脏器纤维化的前提下,推测血清PCⅢ及PⅢNP对早期判断肾积水肾脏纤维化进程具有一定意义。
Objective
This study was to explore the relevance of the changing of collagen typeⅢin serum of obstructive nephropathy and renal fibrosis, then we could elucidate the diagnosis value of serum PCⅢand PⅢNP concentration on the renal fibrosis.
Methods
Thirty patients with hydronephrosis fibrosis were separated to three group:the group of Mild renal fibrosis, Moderate renal fibrosis and Severe renal fibrosis group. Also take 10 cases of renal trauma in patients with renal cell carcinoma as the control group. The serum of each patient was reserved before operation. Collagen typeⅢwas measured by immunohistochemical staining and PCⅢand PⅢNP were measured by radioimmunoassay (RIA). The five renal tissue specimens of each patient were taken out to measure the tubular interstitial lesions by HE staining and to measure the collagenⅢcontents by immunohistochemical SP staining. We analyzed the correlation between the tubular interstitial lesions and the PCⅢand PⅢNP in the serum.
Results
①. PCⅢand PⅢNP in serum of three groups of renal fibrosis in patients with hydronephrosis were higher than the control group, and the value of the PCⅢand PⅢNP in the serum increased gradually with the increasing degree of hydronephrosisi.
②. Interstitial fibrosis in kidneys of patients of hydronephrosis was observed more pronounced than the control groups,and the rate of the tubular interstitial lesions increased gradually with the increasing degree of hydronephrosisi.
③. PCⅢand PⅢNP in serum were positively correlated with the the tubular interstitial lesions.
Conclusions:
①.PCⅢand PⅢNP in serum of three groups of renal fibrosis in patients with hydronephrosis are higher than the control group,and the value of the PCⅢand PⅢNP in the serum increased gradually with the increasing degree of hydronephrosisi. The PCⅢand PⅢNP in serum are correlative with renal interstitial fibrosis in hydronephrosis. PCⅢand PⅢNP in serum can be used to indicate renal fibrosis in hydronephrosis on condition that other organ fibrosis could be excluded.
引文
[1]Am J. United states renal system.Kidney Dis.1996; 18:534-547.
[2]McClellar W M.Epidemiology and risk factors for chronic kidney disease.Med clin North Am,2005,89:419-445.
[3]吴阶平主编.吴阶平泌尿外科学.济南：山东科技出版社,2004,535-540.
[4]McClellar W M.Epidemiology and risk factors for chronic kidney diease. Med clin North Am,2005,89:419-445.
[5]Zeisberg M,Maeshima Y,Mosterman B,et al. Renal fibrosis:Extracellular matrix microenvironment regulates migratory behavior of activated tubular epithelial cells. Am J Pathol,2002,160(6):2001.
[6]Schieppati A, Remuzzi G. Chronic renal diseases aS a public health problem: epidemiology, social, and economic implieations. Kidney Int Suppl,2005, 98:S7-S10.
[7]Kuncio GS, Neilson EG, Haverty T, et al. Mechanisms of tubulointerstitial fibrosis [J]. Kidney Int,1996,49(54):23-27.
[8]Wahl SM, McCartney-Francis N, Mergenhagen SE.Inflammatory and immunomodulatory roles of TGF-beta. Inlmunol Today.1989;10:258-261.
[9]Burgeson RE,Nimni ME. Collagen types Molecular structure and tissue distribution. Clin Orthop Relat Res.1992;(282):250-272.
[10]Yoshiola K, Takemura T, Tohda M, et al Glomerular localization of III collagen in human kidney disease[J].Kidney Int.1989;35:1203-1211.
[11]Vleming LJ, Baelde JJ, Westendorp RGJ, et al. Progression of chronic renal disease in humans is associated with the deposition of basement membrane components and decorin in the interstitial extracelluar matrix [J].Clin Nephrol.1995;4:211-219.
[12]Colombo M, et al. Serum type Ⅲ Procollagen Peptide in alcoholic liver disease and idiopathic hemochromatosis:Its relationship to hepatic fibrosis, activity of the disease and ronoverload HePatolgy.1985;5:475.
[13]林之仑,汤小太,甄宜兰.血清PCⅢ、PⅢNP对肝纤维化的诊断意义。放射免疫学杂志.2000；13：211-212.
[14]Sharma AK, Mauer SM, Kim Y et al. Interstitial fibrosis in obstructive nephropathy. Kidney Int.1993;4:774-778.
[15]Wu K, Setty S, Mauer SM, et al. Altered kidney matrix gene expression in early stage of experimental diabetes. Acta Anat Basel.1997;158:155-165.
[16]Jones CL, Buch S, Post M, et al. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int.1991;40:1020-1031.
[17Keler F, Rehbein C, Schwartz A et al. Increased procollagen in production in patients with kidney disease.Nephron.1988;50:332-337.
[18]Keler F, Lyreal Ser Y, Schuppan D Raised concentrations of the carboxy terminal propeptide of (basement membrane) procolagen (NCI) in serum and urine of patients with glomerulonephritis. Eur J Clin Invest,1992;22:302-308
[19]Hayashi Y, Makino H, Ota Z. Serum and urinary concentrations of type IV collagen and iaminin as a marker of microangiopathy in diabetes. Diabetic Med.1992;9:366-370.
[20]Marder K, Keler F, Schuppan D. Circulation type VI collagen and undulin, in patients with kidney disease, after kidney transp lantation and on hemodialysis. Clin NePhrol.1995;4:178-184.
[21]周永昌,郭万学主编.超声医学(第四版).北京：科学技术文献出版社,2006,1184-1186.
[22]申洪,沈忠英.实用生物体视学技术[M].广州：中山大学出版社,1991.26-80.
[23]Bateman JF, Lamande SR, Ramshaw JAM:Colagen superfamily, in Extracelhilar Matrix (v012):Molecular Components and lnteractio,edited by Comper WD, Amstedam Hanwood Acdemic 1996:22-67.
[24]Krieg T, Leroy EC. Diseases of the extracellular matrix. J M61 Med.1998;76:224-225.
[25]Liu Y. Ep ithelial to mesenchymal transition in renal fibrogenesis:pathologic significance, molecularmechanism, and therapeutic inter2vention. J Am Soc Nephrol,2004,15:1-12.
[26]Eric G Neilson. Mechanisms of Disease:fibroblasts-a new look at an old problem. Nature Clin Prac Nephrol,2006,2(2):101-108.
[27]Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest,2002,110:341-350.
[28]LIU Y. Renal fibrosis:new insights into the pathogenesis and therapeutics[J]. Kidney Int,2006,69:213-217.
[29]Caron A, Desrosiers RR, Langlois S, et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli[J]. Can J Physiol Pharmacol,2005; 83:287.
[30]Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in fight chain-related glomerular damage[J]. Kidney Int,2005; 68:1590.
[31]PortikDobos V, Harris AK, Song W, et al. Endothelin antagonism prevents early EGFR transactivation but not increased matrix metalloproteinase activity in diabetes[J]. Am J Physiol Regul Integr Comp Physiol,2006; 290:R435
[32]陈荣权,陈香美,崔世维,等.组织金属蛋白酶抑制物在老年大鼠肾小管间质病理损害中的动态变化[J].中华老年医学杂志,2004；23(4)：253.
[33]Johnson TS, HaylorJL, Thomas GL, et al.Matrix metalleproteinases and their inhibitions in experimental renal scaring[J].Exp Nep hrol,2002;10(3),182.
[34]Cheng S, Lovett DH. Gelatinase A(MMP-2)is necessary and suficient forrenal tubular cell epithelial-mesenchymal transformation [J]. AM J Pathol,2003; 162: 1937.
[35]Yang J, Shultz RW, Mars WM, et al. Disruption of tissuetype plasminogenactivator gene in mice mduces renal interstltial fibrosis in obstructive nephropathy[J]. J Clin Invest,2002; 110(10):1525.
[36]Zeisberg M, Khurana M, Rao VH, et al. Stage-Specific action of matrixm etalloproteinases influences progressive hereditary kidney disease[J]. PLoS Med,2006; 3(4):e100.
[37]Vuorio E, de Crovmbrugghe B. The family of collagen genes. Annu Rev Biochem.1990;59:837-872.
[38]Rohde H. Radioimmunoassay for type Ⅲ procollagen peptide and its application to human liver disease[J].Eur J Clin Invest.1979;9:451.
[39]李伟道,欧晓娟,叶红军,等.血清Ⅲ型前胶原诊断肝纤维化的临床评价：1199例测定结果分析[J].肝脏病杂志.1995；3：77-79.
[40]彭安国,陈东风,冷思任,等.透明质酸、Ⅲ型胶原、层粘蛋白对肝纤维化诊断价值的研究.中国实用内科杂志.1996；16：49.
[41]Frei A. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with the chronic liver disease [J]. HePatolosy. 1986;10:216.
[42]Kee HX, Thorthil BA, Chevalier RL, et al. Phenotypic transformation of renal tubular epithelial cells and interstitial fibroblasts following unilateral ureteral obstruction (UUO) or single nephron obstruction (SNO) in the rats[J] J Am Soc Nephrol.1996;7:1768-1772.
[43]Imao E, Arai M, Wada A, Suguira T, et al. Phenotypic changes of the mesangial cells induced by overexpression of the TGF-β or PDGF gene into the rat kidney. J Clin Invest,1993;92:2597-2601.
[44]Johnson RJ, Lida H, Alpers CE, et al. Expression of smooth muscle phenotype by rat mesangial cells in immune complex nephritis. J Clin Invest 1991;87:847-858.
[45]Alpers CE, Hudklns KL, Gown AW, et al. Enhanced expression of muscle specific actin in glomerulonephritis. Kidney Int.1992;41:1134-1142.
[46]Macpherson BR, Leslie KO, Lizaso KV, et al.Contractile cells of the kidney in primary glomerular disorders:An immunohistochemnical study using an anti-alpha-smooth muscle actin monoclonal antibody.Hum Pathol.1993; 24: 710-716.
[47]Li JH, Zhu HJ, Huang XR,et al.Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol.2002;13:1464-1472.
[48]Razzaque MS, Haxada T,Taguchi T. Distribution and cellular origin of type Ⅲ, type Ⅳ and type Ⅵ collagens in tubulointerstitial damage in various renal diseases.Clin Nephrol.1996;46:213-215.
[1]WahI SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-beta. Inmmunol Today.1989;10:258-261.
[2]Chen JG. [J]. Foreign Medical Sciences section of Pathophysiology and Clinical Medicine,1991,19 (4):249-251.
[3]Burgeson RE, Nimni ME.Collagen types.Moleular structure and tissue distribution.Clin Orthop Relat Res.1992;(282):250-272.
[4]Vleming LJ,Baelde JJ,Westendorp RGJ et al.Progression of chronic renal disease in humans is associated with the deposition of basement membrane components and decorin in the interstitial extracelluar matrix[J].Clin Nephrol.1995;4:211-219.
[5]林之仑,汤小太,甄宜兰.血清PCⅢ、PⅢNP对肝纤维化的诊断意义.放射免疫杂志.2000；13：211-212.
[6]Liu Y. Ep ithelial to mesenchymal transition in renal fibrogenesis：pathologic significance, molecularmechanism, and therapeutic intervention. J Am Soc Nephrol, 2004,15:1-12.
[7]Eric G Neilson. Mechanisms of Disease:fibroblasts-a new look at an old problem. Nature Clin Prac Nephrol,2006,2(2):101-108.
[8]Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis [J].Clin Invest,2002,110:341-350.
[9]LIU Y. Renal fibrosis:new insights into the pathogenesis and therapeutics[J] Kidney Int,2006,69:213-217.
[10]Caron A, Desrosiers RR, Langlois S, et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli[J]. Can J Physiol Pharmacol,2005; 83:287.
[11]Keeling J,Herrera GA.Matrix metalloproteinases and mesangial remodeling in fight chain-related glomerular damage[J].Kidney Int,2005; 68:1590.
[12]PortikDobos V,Harris AK,Song W,et al.Endothelin antagonism prevents early EGFR transactivation but not increased matrix metalloproteinase activity in diabetes[J].Am J Physiol Regul Integr Comp Physiol,2006;290:R435.
[13]陈荣权,陈香美,崔世维,等.组织金属蛋白酶抑制物在老年大鼠肾小管间质病理损害中的动态变化[J].中华老年医学杂志,2004；23(4)：253.
[14]Johnson TS,HaylorJL,Thomas GL,et al.Matrix metalleproteinases and their inhibitions in experimental renal scaring[J].Exp Nep hrol,2002;10(3),182.
[15]Cheng S,Lovett DH.Gelatinase A(MMP-2) is necessary and suficient forrenal tubular cell epithelial-mesenchymal transformation [J].AM J Pathol,2003;162:1937.
[16]Yang J,Shultz RW,Mars WM,et al.Disruption of tissuetype plasminogenactivator gene in mice mduces renal interstitial fibrosis in obstructive nephropathy[J]. J Clin Invest,2002;110(10):1525.
[17]Zeisberg M,Khurana M,Rao VH,et al.Stage-Specific action of matrixm etalloproteinases influences progressive hereditary kidney disease [J].PLoS Med,2006;3(4):e100.
[18]Friedman SL. Moleculur regulation of hepatic fibrosis, an integrated cellual response to tissue injury[J]. J Biol Chem,2000,275 (11):2247-2250.
[19]查锡良.糖蛋白,蛋白聚糖和细胞外基质.见：周爱儒,主编.生物化学[M].第5版.北京：人民卫生出版社,2001.400-413.
[20]Hohenester E, Engel J. Domain structure and organization in extracullar matrix proteins [J].Matrix Biol,2002,21:115.
[21]Rerolle JP, HertigA,Nguyen G, et al. Plasminogen activator inhibitor-1 is a potential in renal fibrogenesis[J]. Kidney Int,2000,58 (9):1841-1850.
[22]Lemley KV, Wilhelm Kriz. Anatomy of the renal interstitium. Kindey Int.1991;39:370-380.
[23]Stokes MB,Holler S,Cui Y, et al.Expression of decorin, biglycan,and collagen type Ⅰ in human renal fibrosing disease.Kidney lnt.2000;57:487-498.
[24]Groma V. Demonstration of collagen type Ⅵ and alpha-smooth muscle actin in renal fibrotic injury in man. Nephrol Dial Transplant.1998; 13:305-312.
[25]Vuorio E, de Crombrugghe B. The family of collagen genes. Annu Rev Biochem.1990;59:837-872.
[26]Rohde H. Radioimmunoassay for type Ⅲ procollagen peptide and its application to human liver disease [J]. Eur J Clin Invest.1979;9:451.
[27]李伟道,欧晓娟,叶红军,等.血清Ⅲ型前胶原诊断肝纤维化的临床评价：1199例测定结果分析[J]肝脏病杂志.1995；3：77-79.
[28]彭安国,陈东风,冷思任,等.透明质酸、Ⅲ型胶原、层粘蛋白对肝纤维化诊断价值的研究.中国实用内科杂志.1996；16：49.
[29]Frei A. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease[J].Hepatolosy.1986; 10:216.
[30]Coker RK, Laurent JG. Pulmonary fibrosis; cytokine networking in the balance [J].Eur Resp ir J,1998,11 (8):1218-1221.
[31]Diamond JR, Goor HV, Ding G, et al. Myofibroblast in experimental hydronephrosis [J]. Am J Path,1995,146(1):121-129.
[32]Okuda S, Languino LR, Ruoslathi E, et al. Elevated expression of transforming growth factor- β and proteogly can production in experimental glomerulonephritis: possiblerole in expansion of mesangial extracellular matrix [J]. JClin Invest,1990, 86 (2):453-462.
[33]Floege J, Hudkins KL, Seifert RA, et al. Localization of PDGF alpha-receptor in the developing and mature human kidney[J]. Kidney Int,1997,51(4):1140-1150.
[34]Takahiko Nakagawa, Masakiyo Sasahara, Masakazu, Haneda, et al. Role of PDGF B-Chain and PDGF receptors in rat tubular regeneration after acute injury[J]. Am J Pathol,1999,155(5):1689-1699.
[35]Taka yukisuzuki, Masato kimura, Mitsuko asano, et al. Role of atrophic tubules in development of interstitial fibrosis in microembolism-induced renal failure in rat [J]. Am J Pathol,2001,158(1):75-85.
[36]Tang ww, Ulich TR, Lacey DL, et al. Platelet-derived growth factor-β induces renal tubulointerstitial myofibroblastformation and tubulointerstitial fibrosis [J]. Am J Pathol,1996,148:1169-1180.
[37]徐惠,官阳,杨木兰,等.PDGF及PDGFR在大鼠肾间质纤维化过程中的作用.中国现代医学杂志.2007；19：2354-2358.
[38]Sharma AK,Mauer SM,Kim Y et al. Interstitial fibrosis in obstructive nephropathy. Kidney Int.1993;4:774-778.
[39]Wu K,Setty S,Mauer SM,et al. Altered kidney matrix gene expression in early stage of experimental diabetes. Acta Anat Basel.1997;158:155-165.
[40]Jones CL,Buch S,Post M,et al. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int.1991;40:1020-1031.
[41]Kee HX,Thorthil BA,Chevalier RL,et al. Phenotypic transformation of renal tubular epithelial cells and interstitial fibroblasts following unilateral ureteral obstruction (UUO) or single nephron obstruction (SNO) in the rats [J] J Am Soc Nephrol.1996;7:1768-1772.
[42]Imao E,Arai M,Wada A,Suguira T,et al. Phenotypic changes of the mesangial cells induced by overexpression of the TGF-β or PDGF gene into the rat kidney. J Clin Invest,1993;92:2597-2601.
[43]Johnson RJ,Lida H,Alpers CE,et al. Expression of smooth muscle phenotype by rat mesangial cells in immune complex nephritis. J Clin Invest 1991;87:847-858.
[44]Alpers CE,Hudklns KL,Gown AW,et al. Enhanced expression of muscle specific actin in glomerulonephritis. Kidney Int.1992;41:1134-1142.
[45]Macpherson BR,Leslie KO,Lizaso KV,et al.Contractile cells of the kidney in primary glomerular disorders:An immunohistochemnical study using an anti-alpha-smooth muscle actin monoclonal antibody. Hum Pathol.1993;24:710-716.
[46]Li JH,Zhu HJ,Huang XR,et al.Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol.2002;13:1464-1472.
[2]McClellar W M.Epidemiology and risk factors for chronic kidney disease.Med clin North Am,2005,89:419-445.
[3]吴阶平主编.吴阶平泌尿外科学.济南：山东科技出版社,2004,535-540.
[4]McClellar W M.Epidemiology and risk factors for chronic kidney diease. Med clin North Am,2005,89:419-445.
[5]Zeisberg M,Maeshima Y,Mosterman B,et al. Renal fibrosis:Extracellular matrix microenvironment regulates migratory behavior of activated tubular epithelial cells. Am J Pathol,2002,160(6):2001.
[6]Schieppati A, Remuzzi G. Chronic renal diseases aS a public health problem: epidemiology, social, and economic implieations. Kidney Int Suppl,2005, 98:S7-S10.
[7]Kuncio GS, Neilson EG, Haverty T, et al. Mechanisms of tubulointerstitial fibrosis [J]. Kidney Int,1996,49(54):23-27.
[8]Wahl SM, McCartney-Francis N, Mergenhagen SE.Inflammatory and immunomodulatory roles of TGF-beta. Inlmunol Today.1989;10:258-261.
[9]Burgeson RE,Nimni ME. Collagen types Molecular structure and tissue distribution. Clin Orthop Relat Res.1992;(282):250-272.
[10]Yoshiola K, Takemura T, Tohda M, et al Glomerular localization of III collagen in human kidney disease[J].Kidney Int.1989;35:1203-1211.
[11]Vleming LJ, Baelde JJ, Westendorp RGJ, et al. Progression of chronic renal disease in humans is associated with the deposition of basement membrane components and decorin in the interstitial extracelluar matrix [J].Clin Nephrol.1995;4:211-219.
[12]Colombo M, et al. Serum type Ⅲ Procollagen Peptide in alcoholic liver disease and idiopathic hemochromatosis:Its relationship to hepatic fibrosis, activity of the disease and ronoverload HePatolgy.1985;5:475.
[13]林之仑,汤小太,甄宜兰.血清PCⅢ、PⅢNP对肝纤维化的诊断意义。放射免疫学杂志.2000；13：211-212.
[14]Sharma AK, Mauer SM, Kim Y et al. Interstitial fibrosis in obstructive nephropathy. Kidney Int.1993;4:774-778.
[15]Wu K, Setty S, Mauer SM, et al. Altered kidney matrix gene expression in early stage of experimental diabetes. Acta Anat Basel.1997;158:155-165.
[16]Jones CL, Buch S, Post M, et al. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int.1991;40:1020-1031.
[17Keler F, Rehbein C, Schwartz A et al. Increased procollagen in production in patients with kidney disease.Nephron.1988;50:332-337.
[18]Keler F, Lyreal Ser Y, Schuppan D Raised concentrations of the carboxy terminal propeptide of (basement membrane) procolagen (NCI) in serum and urine of patients with glomerulonephritis. Eur J Clin Invest,1992;22:302-308
[19]Hayashi Y, Makino H, Ota Z. Serum and urinary concentrations of type IV collagen and iaminin as a marker of microangiopathy in diabetes. Diabetic Med.1992;9:366-370.
[20]Marder K, Keler F, Schuppan D. Circulation type VI collagen and undulin, in patients with kidney disease, after kidney transp lantation and on hemodialysis. Clin NePhrol.1995;4:178-184.
[21]周永昌,郭万学主编.超声医学(第四版).北京：科学技术文献出版社,2006,1184-1186.
[22]申洪,沈忠英.实用生物体视学技术[M].广州：中山大学出版社,1991.26-80.
[23]Bateman JF, Lamande SR, Ramshaw JAM:Colagen superfamily, in Extracelhilar Matrix (v012):Molecular Components and lnteractio,edited by Comper WD, Amstedam Hanwood Acdemic 1996:22-67.
[24]Krieg T, Leroy EC. Diseases of the extracellular matrix. J M61 Med.1998;76:224-225.
[25]Liu Y. Ep ithelial to mesenchymal transition in renal fibrogenesis:pathologic significance, molecularmechanism, and therapeutic inter2vention. J Am Soc Nephrol,2004,15:1-12.
[26]Eric G Neilson. Mechanisms of Disease:fibroblasts-a new look at an old problem. Nature Clin Prac Nephrol,2006,2(2):101-108.
[27]Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest,2002,110:341-350.
[28]LIU Y. Renal fibrosis:new insights into the pathogenesis and therapeutics[J]. Kidney Int,2006,69:213-217.
[29]Caron A, Desrosiers RR, Langlois S, et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli[J]. Can J Physiol Pharmacol,2005; 83:287.
[30]Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in fight chain-related glomerular damage[J]. Kidney Int,2005; 68:1590.
[31]PortikDobos V, Harris AK, Song W, et al. Endothelin antagonism prevents early EGFR transactivation but not increased matrix metalloproteinase activity in diabetes[J]. Am J Physiol Regul Integr Comp Physiol,2006; 290:R435
[32]陈荣权,陈香美,崔世维,等.组织金属蛋白酶抑制物在老年大鼠肾小管间质病理损害中的动态变化[J].中华老年医学杂志,2004；23(4)：253.
[33]Johnson TS, HaylorJL, Thomas GL, et al.Matrix metalleproteinases and their inhibitions in experimental renal scaring[J].Exp Nep hrol,2002;10(3),182.
[34]Cheng S, Lovett DH. Gelatinase A(MMP-2)is necessary and suficient forrenal tubular cell epithelial-mesenchymal transformation [J]. AM J Pathol,2003; 162: 1937.
[35]Yang J, Shultz RW, Mars WM, et al. Disruption of tissuetype plasminogenactivator gene in mice mduces renal interstltial fibrosis in obstructive nephropathy[J]. J Clin Invest,2002; 110(10):1525.
[36]Zeisberg M, Khurana M, Rao VH, et al. Stage-Specific action of matrixm etalloproteinases influences progressive hereditary kidney disease[J]. PLoS Med,2006; 3(4):e100.
[37]Vuorio E, de Crovmbrugghe B. The family of collagen genes. Annu Rev Biochem.1990;59:837-872.
[38]Rohde H. Radioimmunoassay for type Ⅲ procollagen peptide and its application to human liver disease[J].Eur J Clin Invest.1979;9:451.
[39]李伟道,欧晓娟,叶红军,等.血清Ⅲ型前胶原诊断肝纤维化的临床评价：1199例测定结果分析[J].肝脏病杂志.1995；3：77-79.
[40]彭安国,陈东风,冷思任,等.透明质酸、Ⅲ型胶原、层粘蛋白对肝纤维化诊断价值的研究.中国实用内科杂志.1996；16：49.
[41]Frei A. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with the chronic liver disease [J]. HePatolosy. 1986;10:216.
[42]Kee HX, Thorthil BA, Chevalier RL, et al. Phenotypic transformation of renal tubular epithelial cells and interstitial fibroblasts following unilateral ureteral obstruction (UUO) or single nephron obstruction (SNO) in the rats[J] J Am Soc Nephrol.1996;7:1768-1772.
[43]Imao E, Arai M, Wada A, Suguira T, et al. Phenotypic changes of the mesangial cells induced by overexpression of the TGF-β or PDGF gene into the rat kidney. J Clin Invest,1993;92:2597-2601.
[44]Johnson RJ, Lida H, Alpers CE, et al. Expression of smooth muscle phenotype by rat mesangial cells in immune complex nephritis. J Clin Invest 1991;87:847-858.
[45]Alpers CE, Hudklns KL, Gown AW, et al. Enhanced expression of muscle specific actin in glomerulonephritis. Kidney Int.1992;41:1134-1142.
[46]Macpherson BR, Leslie KO, Lizaso KV, et al.Contractile cells of the kidney in primary glomerular disorders:An immunohistochemnical study using an anti-alpha-smooth muscle actin monoclonal antibody.Hum Pathol.1993; 24: 710-716.
[47]Li JH, Zhu HJ, Huang XR,et al.Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol.2002;13:1464-1472.
[48]Razzaque MS, Haxada T,Taguchi T. Distribution and cellular origin of type Ⅲ, type Ⅳ and type Ⅵ collagens in tubulointerstitial damage in various renal diseases.Clin Nephrol.1996;46:213-215.
[1]WahI SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-beta. Inmmunol Today.1989;10:258-261.
[2]Chen JG. [J]. Foreign Medical Sciences section of Pathophysiology and Clinical Medicine,1991,19 (4):249-251.
[3]Burgeson RE, Nimni ME.Collagen types.Moleular structure and tissue distribution.Clin Orthop Relat Res.1992;(282):250-272.
[4]Vleming LJ,Baelde JJ,Westendorp RGJ et al.Progression of chronic renal disease in humans is associated with the deposition of basement membrane components and decorin in the interstitial extracelluar matrix[J].Clin Nephrol.1995;4:211-219.
[5]林之仑,汤小太,甄宜兰.血清PCⅢ、PⅢNP对肝纤维化的诊断意义.放射免疫杂志.2000；13：211-212.
[6]Liu Y. Ep ithelial to mesenchymal transition in renal fibrogenesis：pathologic significance, molecularmechanism, and therapeutic intervention. J Am Soc Nephrol, 2004,15:1-12.
[7]Eric G Neilson. Mechanisms of Disease:fibroblasts-a new look at an old problem. Nature Clin Prac Nephrol,2006,2(2):101-108.
[8]Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis [J].Clin Invest,2002,110:341-350.
[9]LIU Y. Renal fibrosis:new insights into the pathogenesis and therapeutics[J] Kidney Int,2006,69:213-217.
[10]Caron A, Desrosiers RR, Langlois S, et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli[J]. Can J Physiol Pharmacol,2005; 83:287.
[11]Keeling J,Herrera GA.Matrix metalloproteinases and mesangial remodeling in fight chain-related glomerular damage[J].Kidney Int,2005; 68:1590.
[12]PortikDobos V,Harris AK,Song W,et al.Endothelin antagonism prevents early EGFR transactivation but not increased matrix metalloproteinase activity in diabetes[J].Am J Physiol Regul Integr Comp Physiol,2006;290:R435.
[13]陈荣权,陈香美,崔世维,等.组织金属蛋白酶抑制物在老年大鼠肾小管间质病理损害中的动态变化[J].中华老年医学杂志,2004；23(4)：253.
[14]Johnson TS,HaylorJL,Thomas GL,et al.Matrix metalleproteinases and their inhibitions in experimental renal scaring[J].Exp Nep hrol,2002;10(3),182.
[15]Cheng S,Lovett DH.Gelatinase A(MMP-2) is necessary and suficient forrenal tubular cell epithelial-mesenchymal transformation [J].AM J Pathol,2003;162:1937.
[16]Yang J,Shultz RW,Mars WM,et al.Disruption of tissuetype plasminogenactivator gene in mice mduces renal interstitial fibrosis in obstructive nephropathy[J]. J Clin Invest,2002;110(10):1525.
[17]Zeisberg M,Khurana M,Rao VH,et al.Stage-Specific action of matrixm etalloproteinases influences progressive hereditary kidney disease [J].PLoS Med,2006;3(4):e100.
[18]Friedman SL. Moleculur regulation of hepatic fibrosis, an integrated cellual response to tissue injury[J]. J Biol Chem,2000,275 (11):2247-2250.
[19]查锡良.糖蛋白,蛋白聚糖和细胞外基质.见：周爱儒,主编.生物化学[M].第5版.北京：人民卫生出版社,2001.400-413.
[20]Hohenester E, Engel J. Domain structure and organization in extracullar matrix proteins [J].Matrix Biol,2002,21:115.
[21]Rerolle JP, HertigA,Nguyen G, et al. Plasminogen activator inhibitor-1 is a potential in renal fibrogenesis[J]. Kidney Int,2000,58 (9):1841-1850.
[22]Lemley KV, Wilhelm Kriz. Anatomy of the renal interstitium. Kindey Int.1991;39:370-380.
[23]Stokes MB,Holler S,Cui Y, et al.Expression of decorin, biglycan,and collagen type Ⅰ in human renal fibrosing disease.Kidney lnt.2000;57:487-498.
[24]Groma V. Demonstration of collagen type Ⅵ and alpha-smooth muscle actin in renal fibrotic injury in man. Nephrol Dial Transplant.1998; 13:305-312.
[25]Vuorio E, de Crombrugghe B. The family of collagen genes. Annu Rev Biochem.1990;59:837-872.
[26]Rohde H. Radioimmunoassay for type Ⅲ procollagen peptide and its application to human liver disease [J]. Eur J Clin Invest.1979;9:451.
[27]李伟道,欧晓娟,叶红军,等.血清Ⅲ型前胶原诊断肝纤维化的临床评价：1199例测定结果分析[J]肝脏病杂志.1995；3：77-79.
[28]彭安国,陈东风,冷思任,等.透明质酸、Ⅲ型胶原、层粘蛋白对肝纤维化诊断价值的研究.中国实用内科杂志.1996；16：49.
[29]Frei A. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease[J].Hepatolosy.1986; 10:216.
[30]Coker RK, Laurent JG. Pulmonary fibrosis; cytokine networking in the balance [J].Eur Resp ir J,1998,11 (8):1218-1221.
[31]Diamond JR, Goor HV, Ding G, et al. Myofibroblast in experimental hydronephrosis [J]. Am J Path,1995,146(1):121-129.
[32]Okuda S, Languino LR, Ruoslathi E, et al. Elevated expression of transforming growth factor- β and proteogly can production in experimental glomerulonephritis: possiblerole in expansion of mesangial extracellular matrix [J]. JClin Invest,1990, 86 (2):453-462.
[33]Floege J, Hudkins KL, Seifert RA, et al. Localization of PDGF alpha-receptor in the developing and mature human kidney[J]. Kidney Int,1997,51(4):1140-1150.
[34]Takahiko Nakagawa, Masakiyo Sasahara, Masakazu, Haneda, et al. Role of PDGF B-Chain and PDGF receptors in rat tubular regeneration after acute injury[J]. Am J Pathol,1999,155(5):1689-1699.
[35]Taka yukisuzuki, Masato kimura, Mitsuko asano, et al. Role of atrophic tubules in development of interstitial fibrosis in microembolism-induced renal failure in rat [J]. Am J Pathol,2001,158(1):75-85.
[36]Tang ww, Ulich TR, Lacey DL, et al. Platelet-derived growth factor-β induces renal tubulointerstitial myofibroblastformation and tubulointerstitial fibrosis [J]. Am J Pathol,1996,148:1169-1180.
[37]徐惠,官阳,杨木兰,等.PDGF及PDGFR在大鼠肾间质纤维化过程中的作用.中国现代医学杂志.2007；19：2354-2358.
[38]Sharma AK,Mauer SM,Kim Y et al. Interstitial fibrosis in obstructive nephropathy. Kidney Int.1993;4:774-778.
[39]Wu K,Setty S,Mauer SM,et al. Altered kidney matrix gene expression in early stage of experimental diabetes. Acta Anat Basel.1997;158:155-165.
[40]Jones CL,Buch S,Post M,et al. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int.1991;40:1020-1031.
[41]Kee HX,Thorthil BA,Chevalier RL,et al. Phenotypic transformation of renal tubular epithelial cells and interstitial fibroblasts following unilateral ureteral obstruction (UUO) or single nephron obstruction (SNO) in the rats [J] J Am Soc Nephrol.1996;7:1768-1772.
[42]Imao E,Arai M,Wada A,Suguira T,et al. Phenotypic changes of the mesangial cells induced by overexpression of the TGF-β or PDGF gene into the rat kidney. J Clin Invest,1993;92:2597-2601.
[43]Johnson RJ,Lida H,Alpers CE,et al. Expression of smooth muscle phenotype by rat mesangial cells in immune complex nephritis. J Clin Invest 1991;87:847-858.
[44]Alpers CE,Hudklns KL,Gown AW,et al. Enhanced expression of muscle specific actin in glomerulonephritis. Kidney Int.1992;41:1134-1142.
[45]Macpherson BR,Leslie KO,Lizaso KV,et al.Contractile cells of the kidney in primary glomerular disorders:An immunohistochemnical study using an anti-alpha-smooth muscle actin monoclonal antibody. Hum Pathol.1993;24:710-716.
[46]Li JH,Zhu HJ,Huang XR,et al.Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol.2002;13:1464-1472.