摘要
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1d予喹那普利10mg.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28d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-β1mRNA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-β1mRNA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-β1mRNA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。
Objective To !nvestigate 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-β1 （TGF-β1）in renal tissues were detected by immunohistochemical staining. The local expression of TGF-β1 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-β1, protein were highly expressed in tululointerstitium after UUO operation （P 〈 0. 001 ）. The interstitial volume, TGF-β1 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-β1 mRNA, α-SMA and TGF-β1 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-β1 in impaired kidney, which might decrease the activity of microfibroblasts further.
出处
《中国循证儿科杂志》
CSCD
2010年第1期55-59,共5页
Chinese Journal of Evidence Based Pediatrics
