缺氧诱导因子-1α在实验性大鼠肾间质纤维化过程中的作用  

Effect of hypoxia inducible factor 1-alpha in the process of renal interstitial fibrosis of rats with unilateral ureteral obstruction

作　　者：罗燕萍[1] 李晶[2] 芮金兵[2] 何建强[1] 王晓明[1] 

机构地区：[1]江苏大学附属医院肾脏内科,江苏镇江212001 [2]江苏大学附属医院风湿内科,江苏镇江212001

出　　处：《江苏大学学报（医学版）》2010年第1期6-9,16,I0001,共6页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省社会发展基金资助项目(BS2005043);江苏大学临床医学科技发展基金资助项目(JLY20080010)

摘　　要：目的:观察单侧输尿管梗阻(ulilateral ureteral obstruction,UUO)大鼠模型肾组织中缺氧诱导因子-1α(HIF-1α)的表达,探讨HIF-1α表达水平与肾小管间质纤维化的关系。方法:40只雌性SD大鼠随机分为2组,假手术组,UUO组(每组20只)。制备UUO大鼠模型,术后第7天、第14天处死大鼠,肾组织行HE和Masson染色,免疫组织化学和实时荧光定量PCR(RT-PCR)检测HIF-1α,Ⅰ型胶原(collagenⅠ,ColⅠ)及α-平滑肌肌动蛋白(α-smooth muscleactin,α-SMA)在肾组织中的表达。结果:假手术组与UUO组各时间点肾小管间质纤维化评分比较,差异有统计学意义(P<0.01)。术后HIF-1αmRNA水平随梗阻时间延长而递增。UUO组HIF-1α蛋白表达量随着肾间质损害加重而增加,HIF-1α蛋白主要分布在肾小管,其中以近曲小管表达最明显。HIF-1α表达水平与肾小管间质纤维化评分,α-SMA和ColⅠ的表达水平均存在正相关(R值分别为0.71,0.68,0.82,P均<0.05)。结论:HIF-1α在肾小管上皮细胞内高表达可能参与了肾间质纤维化发生和发展的过程。Objective： To investigate the role of hypoxia inducible factor 1-alpha （HIF-1α）in renal tubulointerstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods： Randomly, 40 female SD rats were divided into sham operation group and UUO group, with 20 in each. The left ureters were exposed, and in the UUO group they were also ligated. On day 7 and 14, some of the kidneys were harvested to study in them the expressions of renal tubular interstitial fibrosis, the expressions of mRNAs of HIF-1 α, α-smooth muscle actin（α-SMA） and collagen I （ Col I ） with RT-PCR and the expressions of these proteins immunohistochemically. Results： Compared with sham group, the scores of renal interstitial fibrosis in UUO rats were higher significantly. HIF-1 αmRNAs increased with time after operation in the kidneys in the UUO rats. And the protein expression of HIF-1α increased in the kidneys obtained on the 14th day after operation. Immunohistochemically HIF-1α mainly expressed in renal tubular epithelial cells, especially in proximal tubular cells. The renal tubulointerstitial expression of HIF-1 α was positively associated with the scores of renal interstitial fibrosis and the expression ofα-SMA and Col I . Conclusion： HIF-1α may play an important role in mediating the renal tubulointerstitial fibrosis.

关 键 词：缺氧诱导因子-1Α 肾间质纤维化 单侧输尿管梗阻 

分 类 号：R693[医药卫生—泌尿科学]