The mechanism of renal interstitial fibrosis after unilateral ureteral obstruction in rats and effects of enalapril on the process
DENG Yueyi ,CHEN Yiping ,HU Zhongyi
(Department of Nephrology,Longhua Hospital,Shanghai Chinese Medicine University,Shanghai 200032, China)
Abstract:Objective To study the mechanism of renal interstitial fibrosis after unilateral ureteral Obstruction and effects of enalapril on the process of the fibrosis.Methods Five days after UUO animal models were made.Immunohistochemistry was applied to measured collagen Ⅰ,Ⅲ,Ⅳ α-SMA and the number of infiltrating T lymphocytes in the renal interstitium; In the same time,expression of TGF-β1 mRNA and TIMP-1 mRNA in the obstructed kidney were analyzed with RT-PCR.Results Collagen Ⅰ,Ⅲ,Ⅳ in the influenced tissues remarkbly increased.In cmnparison with the model group,the enalapril group had less deposition of collagen Ⅰ,Ⅲ,Ⅳ (P<0. 001).In addition,enalapril could significantly decrease the number of infiltrating CD8 +T lymphocytes (P<0.01) in the renal interstitial tissue and sharply lower the over-expression of α-SMA, TGF-β1 mRNA and TIMP-1 mRNA caused by ureteral obstruction (P<0. 01).Conclusions After ureteral obstruction, CD8+T lymphocytes infiltrate into the renal interstitium and the expressions of α-SMA, TGF-β1 mRNA and TIMP-1 mRNA increase,which consequently results in a remarkable increaseing deposition of collagen Ⅰ,Ⅲ,Ⅳ in the renal interstitium.Enalapril possesses inhibitory effects on the above procedure.
Keywords:Fibrosis; Angiotensin converting enzytne inhibitor;Renal interstitium参考文献:
[1]Marcussen N.A tubular glomemli and the structural basis for chronic renal failure.Lab Invest,1992,66:265-284.
[2]Morrissey J J,Ishidoya S,McCraeken It,et al.Nitric oxide generation ameliorates the tubulointerslilial fibrosis of obstructive nephropathy.JASN,1996,7:2202-2212.
[3]赵涵芳,程枫,章有章.用RT-PCR方法检测烧伤愈合时生长因子的表达.上海第二医科大学学报, 1995,15 Suppl:37-42.
[4]Kaneto H.Morrissey J,McCracken R.et al.Eualapril reduces collagen type Ⅳ synthesis and expansion of the interstitium in the obstructed kidney of the rat.Kidney Int,1994,45:1637-1647.
[5]张明,郭慕依,陈琦,等.大鼠肾小球系膜细胞培养.上海医科大学学报,1995,22:207-209.
[6]Taipale J,Sahafinen J,Hedman K,el al.Latent transfimning growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils.J Histochem Cytochem,1996,44:875-889.
[7]Fong TAT,Mosmann TR.Alloreactive murine CD8+T cell clones secrete the Th1 pattern of cytokines.J Immunol,1990,144:1774-1752.
[8]Takada M,Chandraker A,Nadeau KC,et al.The role of the B7 costimulatory pathway in experimental cold ischemia-reperfusion injury.J Clin Invest,1997,100:1199-1203.
[9]Chandraker A,Takada M,Nadeau KC,et al.CD28-B7 blockade in organ dysfunction secondary to cold ischemia/reperfusion injury.Kidney Int,1997,52:1678-1684.
[10]Norman JT,Lewis MP.Matrix metalloproteinases (MMPs) in renal fibrosis.Kidney Int.1996,49 Supple 54 S61-S63.
[11]Engelmyer E,van Goof H, Edwards DR,et al.Differential mRNA expression of renal cortical tissue inhibitor of metalloproteinase-1,-2,and-3 in experimental hydronephrosis.JASN,1995,5:1675-1683.
[12]Sharma AK,Mauer SM,Kim Y,et al.Altered expression of matrix metalloproteinase-2,TIMP,and TIMP-2 in obstructive nephropathy.J Lab Clin Med,1995,125:754-761.
收稿日期:1999-08-15
