喹那普利对单侧输尿管结扎大鼠肾纤维化拮抗作用的研究

目的 研究喹那普利对梗阻性肾病肾间质纤维化的影响及其机制。方法 30只SD大鼠随机分为3组：假手术组（n＝6）、单侧输尿管结扎(UUO)组（n＝12）和喹那普利组（n＝12）。喹那普利组在UUO术前1 d予喹那普利10 mg·kg-1·d-1 灌胃，假手术组及UUO组予同等体积生理盐水灌胃。各组大鼠分别于术后14和28 d取梗阻侧肾组织。采用Masson染色及免疫组化方法观测各组大鼠的肾间质容量、肾组织α-平滑肌肌动蛋白（α-SMA）及转化生长因子-β1（TGF-β1）蛋白水平的变化。以原位杂交法检测各组大鼠肾组织TGF-β1 mRNA表达的变化。结果 与假手术组比较，UUO组大鼠肾小管明显萎缩塌陷或极度扩张，伴肾间质增生，输尿管梗阻后4周时上述病理改变尤为明显，肾间质容量明显升高(P<0.001)。免疫组化染色检测结果显示，UUO组α-SMA及TGF-β1蛋白水平均明显高于假手术组，且随梗阻时间的延长呈进行性升高(P<0.001)。原位杂交结果表明，UUO组TGF-β1 mRNA在肾小管间质中的表达显著高于假手术组(P<0.001)。喹那普利组肾间质容量、肾小管间质中TGF-β1 mRNA表达、TGF-β1蛋白和α-SMA水平均显著低于UUO组(P<0.05或<0.01)。结论 喹那普利可明显抑制肾组织分泌TGF-β1，可能的机制之一是减少其下游效应细胞-肌纤维母细胞的活化，从而减缓UUO大鼠肾纤维化进程。

Quinapril ameliorates renal fibrosis in unilateral ureteral obstruction rats

Objective To investigate the quinapril resistant effect and its machenism on renal fibrosis of obstructive nephropathy.Methods Thirty Sprague-Dawley rats were randomly assigned to the sham group (n=6), unilateral ureteral obstruction (UUO) operation group(n=12)or quinapril treatment (10 mg·kg~(-1)·d~(-1)) + UUO operation group (n=12). The renal tissues from each group were collected 14 or 28 days after operation. The interstitial fibrosis was evaluated by Masson＇s trichrome staining. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β_1(TGF-β_1 )in renal tissues were detected by immunohistochemical staining. The local expression of TGF-β_1 mRNA was detected by in situ hybridization.Results Compared with the sham group, the renal pathological changes displayed a spectrum of changes of tubular atrophy, tubular dilation and interstitial fibrosis in UUO group. These changes were more obvious in the late stage kidney on UUO group(observed on 4 weeks after opration). The renal interstitial volume was increased after UUO operation based on the results of Masson＇s trichrome staining (P<0.001). The results of immunohistochemical staining showed that α-SMA and TGF-β_1 protein were highly expressed in tululointerstitium after UUO operation (P<0.001). The interstitial volume, TGF-β_1 and α-SMA protein were expressed more abundantly in UUO group 4 weeks after the obstrution. High expression of TGF-β1 mRNA in UUO group was detected by in situ hybridization assay at 2 and 4 weeks time-points after operation (P<0.001). Quinapril treatment successfully inhibited the increasing tendency of interstitial volume, TGF-β_1 mRNA, α-SMA and TGF-β_1 protein, though failed to reverse completely (P<0.05 or <0.01).Conclusions Quinapril could delay the progression of renal fibrosis in UUO rats. One of the possible machenisms was that quinapril inhibited the secretion of TGF-β_1 in impaired kidney, which might decrease the activity of microfibroblasts further.