摘要
目的观察福辛普利对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾脏转化生长因子β激活激酶(TGF-activated kinase1,TAK1)表达的影响,及其对肾间质纤维化(renal interstitial fibrosis,RIF)的保护作用。方法采用单侧输尿管结扎术致RIF大鼠模型。72只大鼠按随机数字表法分为3组:假手术组、UUO模型组及福辛普利治疗组,每组24只。治疗组于术后2d给予福辛普利10mg/(kg.d)灌胃,假手术组与模型组每天给予等量生理盐水灌胃。各组分别于术后7、14、21d处死8只大鼠,采用HE及Masson染色观察梗阻侧肾脏病理变化,原位杂交、RT-PCR及Western blot检测肾组织TAK1的表达。结果模型组大鼠梗阻侧肾脏肾小管间质损伤指数明显高于同期假手术组(P<0.05),福辛普利干预后肾小管间质损伤指数明显降低(P<0.05);TAK1mRNA和蛋白表达情况:模型组各时间段TAK1表达升高,且随着病理损害的进展呈现下降趋势,但表达量仍显著高于同期假手术组(P<0.05),经福辛普利干预后表达显著下降(P<0.05)。结论福辛普利可能通过下调TAK1表达,从而减轻UUO术后肾组织间质纤维化的病程进展。
Objective To investigate the effect of fosinopril on the expression of transforming growth factor （TGF）-activated kinase 1 （TAK-1） in the kidney of rats with unilateral ureteral obstruction （UUO）,and its protective effect on renal interstitial fibrosis （RIF）.Methods UUO model was induced by ligating the left ureter in rats.A total of 72 male Sprague-Wistar rats were randomly divided into 3 groups：sham-operated group （n=24）,UUO model group （n=24） and UUO＋fosinopril group （n=24）.The rats were treated with 10 mg/（kg·d） by gastric gavage in the fosinopril treated group from 2 d after the operation,and the rats were treated with the identical dose of normal saline in the other 2 groups.Eight rats of each group were sacrificed at 7,14 and 21 d after UUO.Pathological changes of the renal tissue were observed by HE and Masson staining,and the mRNA and protein expression of TAK1 was detected by in situ hybridization,real-time PCR and Western blot analysis.Results The renal interstitial damage index of UUO group was increased compared with that of the sham-operation group （P0.05）,but was decreased in fosinopril treatment group （P0.05）.The protein expression of TAK1 and its mRNA in UUO group were up-regulated compared with those in the sham-operation group （P0.05）,but decreased in fosinopril treatment group at the same time points （P0.05）.Conclusion Fosinopril may play a protective role in the kidney and alleviate RIF after UUO by down-regulating the expression of TAK1.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第9期954-958,共5页
Journal of Third Military Medical University
