摘要
目的通过被动型Heymann肾炎(PHN)大鼠模型,观察来氟米特对肾组织Wilms瘤抑癌因子(WT-1)表达及蛋白尿的影响。方法Wistar大鼠随机分为PHN组、来氟米特组和对照组。尾静脉注射抗FX1A血清,建立PHN模型。于实验第4、8、12周末,BCA法检测24h尿蛋白含量,光镜、电镜观察肾组织病变,WesternBlot检测肾组织WT-1蛋白表达。结果与对照组比较,PHN组从第4周末起,来氟米特组从第8周末起,24h尿蛋白均增多(P<0.01);来氟米特组24h尿蛋白均低于同时间点的PHN组(P<0.01)。光镜、电镜检查来氟米特组肾脏病变程度轻于PHN组。第4周末PHN组和来氟米特组WT-1表达均明显低于对照组(P<0.01);PHN组WT-1表达渐减少,来氟米特组WT-1表达渐增多;12周末来氟米特组WT-1表达多于PHN组(P<0.01),但仍低于对照组。结论来氟米特可能是通过上调足细胞WT-1表达,维持足细胞功能,对PHN起到治疗作用。
Objective To study the effect of leflunomide on Wilms＇ tumor suppressor-1 （WT-1） expression of renal tissues and on proteinuria in rats with passive Heymarm nephritis. Methods Forty-five male Wistar rats were randomly assigned into passive Heymann nephritis group （group PHN）, leflunomide-treated passive Heymarm nephritis group （group L） and control group（C）. The PHN model was induced by injection of anti-FXlA serum through the tail vein. The rats in group L ware given leflunomide daily by garages, and those in group PHN and group C were adminstered norreal saline by the same approach. At the end of the 4 th,8th and 12 th week after injection, urine specimens of five rats in each group were collected for 24 hours for detecting 24-h urinary protein. Then the rats were sacrificed and the kidneys were acquired for histological study under light microscope and electronic microscope. Western blot was used to detect the WT-1 expression of renal tissues. Results At the end of the 4th week, the 24-h urinary protein of group PHN was higher than that of group C （P〈0. 01） ,-and that of group L at the end of the 8 th week （P〈0. 01）. Both of them gradually increased. The 24-h urinary protein of group L was always lower than that of group PHN（P〈 0. 01）. Histological study under light microscopa and electronic microscope demonstrated that leflunomide reduced glomerular lesions of the rat with PHN. At the end of the 4 th week, the WT-1 expressions of group PHN and group L were lower than those of group C（P〈0. 01）. The WT-1 expression of group L gradually increased. At the end of the 12 th week, the WT-1 expression of group L was higher than that of group PHN（P〈0. 01）, but still lower than that of group C. Conclusion Leflunomide has a suppressive effect on PHN possibily through up-regulation of WT-1 in the podocyte.
出处
《江苏医药》
CAS
CSCD
北大核心
2007年第2期171-174,共4页
Jiangsu Medical Journal
基金
江苏省医学重点人才工程基金(RC2002045)
江苏省自然科学基金(BK2003109)
