单侧输尿管梗阻后肾间质纤维化的产生机制及依那普利对其调节作用
作者：邓跃毅 陈以平 胡仲仪 赵仲华
单位：邓跃毅(200032 上海中医药大学附属龙华医院肾内科)；陈以平(200032 上海中医药大学附属龙华医院肾内科)；胡仲仪(200032 上海中医药大学附属龙华医院肾内科)；赵仲华(上海医科大学病理学教研室)
关键词：纤维化；血管紧张素转换酶抑制药；肾间质
中华肾病杂志000408摘 要：目的 研究单侧输尿管梗阻后肾间质纤维化发生机理及血管紧张素转换酶抑制剂依那普利对其的调节作用。方法 采用单侧输尿管结扎模型，造模5 d后用免疫组织化学法观察梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原，α-平滑肌肌动蛋白(α-SMA)的表达，T淋巴细胞浸润数；用逆转录聚合酶链反应(RT-PCR)法观察梗阻肾组织转化生长因子β1(TGP-β1)Mrna、组织基质金属蛋白酶抑制物-1(TIMP-1)Mrna的表达。结果 模型组及依那普利组梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原均明显增加，依那普利组比模型组的Ⅰ、Ⅲ、Ⅳ型胶原沉积减少(P<0.001)，依那普利能明显减少肾间质中浸润的CD8+T淋巴细胞数 (P<0.01)，显著降低因输尿管结扎导致过度表达的α-SMA、TGP-β1mRNA、TIMP-1mRNA(P<0.01)。结论 输尿管梗阻后CD8+T淋巴细胞浸润肾间质，α-SMA、TCF-βmRNA、TIMP-1mRNA表达增加，导致梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原均明显增加，依那普利对其有一定的抑制作用。
, 百拇医药
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.
, 百拇医药
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.
, 百拇医药 [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.
, http://www.100md.com
[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.
, 百拇医药
[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, http://www.100md.com
单位：邓跃毅(200032 上海中医药大学附属龙华医院肾内科)；陈以平(200032 上海中医药大学附属龙华医院肾内科)；胡仲仪(200032 上海中医药大学附属龙华医院肾内科)；赵仲华(上海医科大学病理学教研室)
关键词：纤维化；血管紧张素转换酶抑制药；肾间质
中华肾病杂志000408摘 要：目的 研究单侧输尿管梗阻后肾间质纤维化发生机理及血管紧张素转换酶抑制剂依那普利对其的调节作用。方法 采用单侧输尿管结扎模型，造模5 d后用免疫组织化学法观察梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原，α-平滑肌肌动蛋白(α-SMA)的表达，T淋巴细胞浸润数；用逆转录聚合酶链反应(RT-PCR)法观察梗阻肾组织转化生长因子β1(TGP-β1)Mrna、组织基质金属蛋白酶抑制物-1(TIMP-1)Mrna的表达。结果 模型组及依那普利组梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原均明显增加，依那普利组比模型组的Ⅰ、Ⅲ、Ⅳ型胶原沉积减少(P<0.001)，依那普利能明显减少肾间质中浸润的CD8+T淋巴细胞数 (P<0.01)，显著降低因输尿管结扎导致过度表达的α-SMA、TGP-β1mRNA、TIMP-1mRNA(P<0.01)。结论 输尿管梗阻后CD8+T淋巴细胞浸润肾间质，α-SMA、TCF-βmRNA、TIMP-1mRNA表达增加，导致梗阻肾间质Ⅰ、Ⅲ、Ⅳ型胶原均明显增加，依那普利对其有一定的抑制作用。
, 百拇医药
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.
, 百拇医药
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.
, 百拇医药 [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.
, http://www.100md.com
[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.
, 百拇医药
[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, http://www.100md.com