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目的 研究单侧输尿管梗阻后肾间质纤维化的发生机理及血管紧张素转换酶抑制剂苯那普利对其保护作用。方法 将 2 4只大鼠随机分为假手术组即对照组、手术组和苯那普利组 ,采用单侧输尿管梗阻 (UUO)模型 ,术后 2周观察梗阻肾组织病理改变 ,应用免疫组织化学方法检测肾间质Ⅲ型胶原 ,转化生长因子 β1(TGF -β1)和核因子—kB(NF kB)的表达。并应用放射免疫法检测血浆和肾组织血管紧张素Ⅱ (AngⅡ )的含量。结果 手术组肾间质Ⅲ型胶原 ,TGF - β1和NF kB的表达增加 ,血浆和肾组织AngⅡ增高 ,与对照组相比有显著差异 (P<0 0 5 )。苯那普利组与手术组相比Ⅲ型胶原、TGF - β1、NF kB的表达下调 ,AngⅡ减少 ,差异显著 (P <0 0 5 )。结论 苯那普利可能通过阻断AngⅡ的作用和抑制TGF - β1、NF kB的过度表达 ,使肾间质Ⅲ型胶原沉积减少而产生保护肾脏作用。
Objective To study the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction and the protective effect of benazepril, an angiotensin converting enzyme inhibitor. Methods Twenty-four rats were randomly divided into sham-operation group, control group, operation group and benazepril group. Unilateral ureteral obstruction (UUO) model was used. The pathological changes of obstructed kidney were observed 2 weeks after operation. The expressions of type Ⅲ collagen, transforming growth factor β1 (TGF-β1) and nuclear factor-kB (NF kB) in renal interstitium were detected by chemical methods. The contents of angiotensin Ⅱ (AngⅡ) in plasma and kidney tissue were detected by radioimmunoassay. Results The expression of type Ⅲ collagen, TGF - β1 and NF kB in the renal interstitium was increased in the operation group, while the Ang Ⅱ in the plasma and renal tissues was increased. There was a significant difference (P <0.05) compared with the control group. Compared with the surgery group, the expression of type Ⅲ collagen, TGF - β1 and NF kB in the benazepril group was decreased and the Ang Ⅱ decreased, with significant difference (P <0.05). Conclusion Benazepril may protect the kidneys by blocking the effect of Ang Ⅱ and inhibiting the overexpression of TGF - β1 and NF kB, thereby reducing the deposition of type Ⅲ collagen in renal interstitium.