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卢守燕,刘明龙,刘天喜,李建华.福辛普利对肾间质纤维化大鼠转化生长因子β激活激酶表达的下调作用[J].陆军军医大学学报(原第三军医大学学报),2010,32(09):954-958.
Lu Shouyan,Liu Minglong,Liu Tianxi,Li Jianhua.Fosinopril down-regulates transforming growth factor-activated kinase 1 in rats with renal tubulointerstitial fibrosis[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(09):954-958.
卢守燕,刘明龙,刘天喜,李建华.福辛普利对肾间质纤维化大鼠转化生长因子β激活激酶表达的下调作用[J].陆军军医大学学报(原第三军医大学学报),2010,32(09):954-958. DOI:
Lu Shouyan,Liu Minglong,Liu Tianxi,Li Jianhua.Fosinopril down-regulates transforming growth factor-activated kinase 1 in rats with renal tubulointerstitial fibrosis[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(09):954-958. DOI:
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 kinase 1,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2 d给予福辛普利10 mg/(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、21 d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(P0.05),福辛普利干预后肾小管间质损伤指数明显降低(P0.05);TAK1 mRNA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(P0.05),经福辛普利干预后表达显著下降(P0.05)。 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.
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