摘要
目的建立兔慢性肾功能衰竭模型,为干细胞移植治疗和相关研究奠定基础。方法普通级大耳白兔随机分为正常对照组和单侧输尿管结扎(unilateral ureteral obstruction,UUO)组。UUO组于输尿管结扎后2、4、6、8周进行血生化肾功能指标检测,并取肾组织观察肾脏病理学改变,通过SPECT动态观察肾小球滤过率的变化,采用免疫组织化学方法观察肾组织转化生长因子-β1(TGF-β1)的表达情况。结果①UUO组术后第2周,出现明显的血肌酐升高,尿素氮术后第8周开始升高(P<0.01)。②UUO组术后第4周,肾脏组织出现了早期间质纤维化的病理改变,术后第8周肾小球开始出现硬化,间质纤维化明显,皮质明显变薄。术后第12周,肾小球硬化比例增加,肾小管玻璃样变性,间质纤维化进一步加重(P<0.05)。③SPECT动态观察肾小球滤过率,UUO组第4周GFR值比正常对照组降低,到第8周时,GFR值进一步下降,结扎侧肾脏功能降低甚至丧失。④免疫组织化学染色显示,TGF-β1在术后第4、8、12周均明显增强,并且各时间点表达均有显著差异(P<0.05)。结论单侧输尿管结扎法成功制作比较稳定的慢性肾功能不全模型,UUO后第8周符合肾脏间质纤维化模型标准。
Objective To establish the rabbit model of chronic renal failure by unilateral ureteral obstruction (UUO). Then to prove renal tubulointerstitial fibrosis can be induced ideally. Methods Normal rabbits were randomly divided into normal control group and UUO group. Detecting blood biochemical indicators of renal function at each time point,and pathological changes in the renal interstitial,monitoring of glomerular filtration rate by SPECT. Analysis of the expression of TGF-β1 showed by immunohistochemistry. Results UUO after the first 2 weeks,Scr increased and BUN did not change significantly. At 8 weeks Scr and BUN increased ( P〈0. 01). The first 4 weeks as early as during the performance of interstitial fibrosis,at 8 weeks glomerular sclerosis began to appear and interstitial fibrosis increased (P〈0. 05). The first 4 weeks of GFR in UUO group lower than the normal group,to the first 8 weeks of GFR in UUO decreased significantly and glomerular filtration function was lost. Immunohisto-chemistry showed that TGF-β1 had a scanty expression in the normal group. The expression at 4,8 and 12 weeks had a significant increase (P〈0. 05). Conclusion UUO is a more stable model,and the first 8 weeks in UUO group would be an ideal time of renal interstitial fibrosis in animal model.
出处
《中国比较医学杂志》
CAS
2010年第10期48-51,89,共5页
Chinese Journal of Comparative Medicine
基金
云南省科技计划重点项目资助资助号:2003C013Z
关键词
单侧输尿管结扎
肾间质纤维化
模型
动物
Unilateral ureteral obstruction(UUO)
Renal interstitial fibrosis
Model
animal