摘要
目的探讨外源性尿激酶型纤溶酶原激活物(uPA)对环孢素A(CsA)致慢性肾病大鼠肾间质炎症的干预作用。方法将雄性SD大鼠低盐饮食饲养,经口服灌胃CsA(25mg/kg·d)4周,制作慢性CsA肾病模型,分别给予小剂量uPA持续干预和大剂量uPA间断干预。4周末,观察大鼠血肌酐(Scr)、尿素氮(BuN)及24h尿蛋白的变化,Masson染色观察肾组织纤维蛋白沉积,免疫组化检测肾间质ED-1阳性巨噬细胞浸润数量、肾组织uPA及转化生长因子b1(TGF-β1)的表达。结果大鼠经CsA灌胃后,Scr、BuN升高,24h尿蛋白增加,肾间质纤维蛋白沉积增多,巨噬细胞浸润数量增加,肾局部uPA含量下降以及肾组织TGF-β1表达上调,表明大鼠肾间质炎症模型建立成功。小剂量uPA持续给药血Scr、BuN、24h尿蛋白水平下降(P<0.01或P<0.05),肾间质纤维蛋白沉积和炎性细胞浸润减轻(P<0.05),uPA表达增加(P<0.05),肾组织TGF-β1表达降低(P<0.05)。大剂量uPA间断干预生化指标无显著性差异,局部uPA轻度升高,但对减轻肾小管间质纤维化和下调TGF-β1表达无显著性差异(P>0.05)。结论小剂量uPA持续干预能有效减轻CsA慢性肾病大鼠肾间质纤维蛋白沉积、炎性细胞浸润及下调肾组织TGF-β1表达,从而减轻肾脏炎症反应和纤维化,为其临床应用提供了基础。
Objective To investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A（CsA）-indnced nephropathy. Methods Male SD rats were fed on low salt diet （0.05% sodium） for 7 days and randomized into 4 groups for treatment with CsA, CsA＋continuous low-dose uPA （U2）, intermittent CsA＋ high-dose uPA （U6） or vehicle （control group）. In the former 3 groups, the rats were subjected to daily intragastric administration of CsA （25 mg/kg） for 4 weeks to establish CsA-indnced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator （uPA） and transforming growth factor-β1 （TGF-β1）. Results Four weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine （Scr）, blood urea nitrogen （BUN） and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-β1 expression in the renal tissue, which were significantly reduced in U2 group （P〈0.05） but not in U6 group （P〉0.05）. Conclusion Continuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number ofmacrophages and TGF-β1 expression in the renal tissue.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第5期835-838,共4页
Journal of Southern Medical University
关键词
环孢素A
慢性肾病
尿激酶
巨噬细胞
转化生长因子-Β1
小管间质纤维化
cyclosporine A
chronic kidney disease
urokinase
macrophags
transforming growth factor-β1
renal interstitial fibrosis
