摘要
目的观察尿酸性肾病大鼠肾脏血小板反应蛋白-1(TSP-1)和缺氧诱导因子-1α(HIF-1α)的表达及缬沙坦对其影响,探讨缬沙坦对尿酸性肾病大鼠肾间质纤维化的干预机制。方法选取雄性健康Wistar大鼠36只为研究对象,适应性喂养1周后,采用随机数字表法分为正常组、模型组和缬沙坦组,每组12只。采用酵母和腺嘌呤建立尿酸性肾病模型,造模同时给予缬沙坦干预。于入组3周和5周时观察3组大鼠血尿酸(UA)、血肌酐(Scr)及肾脏病理变化,采用免疫组织化学法和逆转录聚合酶链反应(RT-PCR)法检测肾脏TSP-1和HIF-1α的表达。结果 3组大鼠3周和5周时测得的体质量、UA、Scr水平比较,差异均有统计学意义(P<0.05)。模型组和缬沙坦组大鼠3周、5周时的体质量低于正常组大鼠,UA、Scr水平高于正常组大鼠,差异均有统计学意义(P<0.05);模型组大鼠3周和5周时的体质量低于缬沙坦组,Scr水平高于缬沙坦组,差异均有统计学意义(P<0.01)。3组大鼠3周和5周时RT-PCR测得的TSP-1 mRNA、HIF-1αmRNA表达量比较,差异均有统计学意义(P<0.05)。模型组和缬沙坦组3周和5周时TSP-1 mRNA、HIF-1αmRNA的表达量均高于正常组(P<0.01),模型组3周和5周时TSP-1 mRNA、HIF-1αmRNA的表达量亦均高于缬沙坦组,差异有统计学意义(P<0.05)。模型组大鼠3周和5周时肾组织TSP-1 mRNA与HIF-1αmRNA的表达分别呈正相关(r值分别为0.821和0.736,P<0.05)。结论尿酸性肾病的发展存在缺氧状态;缬沙坦可能通过下调TSP-1及HIF-1α的表达改善肾脏纤维化程度。
Objective To investigate the expression of thrombospondin - 1 （ TSP - 1 ） and hypoxia - inducible factor - 1α （ HIF -1α） in uric acid nephropathy rats and the effect of Valsartan in order to understand the intervention mechanism of Valsartan on renal interstitial fibrosis. Methods 36 male Wistar rats were selected and were randomly divided into normal group, model group and valsartan group with each group 12 rats. Yeast and adenine were used to establish uric acid nephropathy, and meanwhile, valsartan intervention was also performed. After three and five weeks, UA, Scr and renal histological changes were observed. Immunohistochemieal method and RT - PCR method was used to detect the expression of TSP - 1 and HIF - 1α. Results The body weight, UA and Set between the three groups at three and five weeks all showed statistically significant differ- ences （ P 〈 0. 05 ） . The body weight of model group and valsartan group at three and five weeks was significantly lower than the normal group, while the UA and Ser were significantly higher than the normal group （ P 〈 0. 05 ） . The body weight of the model group at three and five weeks was significantly lower than the valsartan group, while the Scr was significantly higher than the val- sartan group （ P 〈 0. 01 ） . The expression of TSP - 1 mRNA and HIF - 1 α mRNA detected by RT - PCR at three and five weeks between the three groups showed statistically significant differences （ P 〈 0. 05 ） . The expression of TSP - 1 mRNA and HIF - 1 α mRNA in model group and valsartan group at three and five weeks were significantly higher than the normal group （ P 〈 0. 01 ） , and the expression of TSP - 1 mRNA and HIF - 1α mRNA in model group was significantly higher than the valsartan group （ P 〈 0.05） . The expression of TSP- 1 mRNA and HIF-1α mRNA in model group at three and five weeks was positively correlated （ r = 0. 821 and 0. 736, P 〈 0. 05 ） . Conclusion The hypoxia condition exists in uric acid nephropathy rats. Valsartan can im- prove renal interstitial fibrosis by decreasing the expression of TSP - 1 and HIF - 1α.
出处
《中国全科医学》
CAS
CSCD
北大核心
2013年第6期644-648,共5页
Chinese General Practice
