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

The mechanism of renal interstitial fibrosis after unilateral ureteral obstruction in rats and effects of enalapril on the process

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５ｄ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（ＴＧＦ－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ＣＤ＋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、ＴＧＦ－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；ＴＧＦ－β１ｍＲＮＡ、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。

Objective To study the mechanism of renal interstitial fibrosis after unilateral ureteral Obstruction and effects of enalapril on the process of the fibrosis. Methotls 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-βI 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 comparison 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-ｓSMA, TGF-β1 mRNA and TJMP-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.