The Expression And Significance Of Hypoxia-inducible Factor-1αin Renalinterstitial Fibrosis

Objective:To investigate the role of hypoxia-inducible factor-1a (HIF-la) on renal fibrosis.Methods:60 Sprague-Dawley male rats were randomly divided into sham-operated rats group (SOR group) and ulilateral ureteral obstruction model group (UUO group).Ten rats were killed 3,7,and 14 days after operation respectively,the dynamic histological changes of renal interstitial tissues were observed on HE stained tissue sections. The expression of protein and mRNA of HIF-la、CTGF、TGF-β1 were assayed by immunohistochemistry and real time polymerase chain reaction.Results:(1)HE stain:Renal damage was exacerbated in UUO group compared with those of sham group. At 3th day after UUO, the renal interstitial edema was found, tubular expanded and inflammatory cells existed in tubulointerstitial. The change became obviously at the 7 th day:interstitial obviously widend,expansion had degenerated, had odema and some even died, on the 14 th day, substantial inflammatory cell infiltrated and renal interstitial fibrosis aggravated. (2)immunohistochemistry:the protein expression of HIF-1a、CTGF and TGF-β1 were all significantly increased in UUO group compared with those of sham group? HIF-1a and CTGF were mainly expressed in renal tubular epithelial cells and renal interstitial cells, TGF-B1 was mainly expressed in renal interstitial cells.(3)RT-PCR:HIF-lamRNA level began to increase as early as 3 day after UUO, this increase were followed by the elevation of CTGFmRNA and TGF-β1 mRNA,which significantly increased compared with those of sham group (P<0.05). (4)Correlation:There were positive correlation between the expression of HIF-lamRNA and CTGFmRNA、TGF-β1 mRNA in UUO 3 days(r=0.748,0.659 P<0.05). There were positive correlation between the expression of HIF-lamRNA and CTGF mRNA、TGF-βlmRNA in UUO 7 days (r=0.663,0.645 P<0.05). There were positive correlation between the expression of HIF-lamRNA and CTGFmRNA, TGF-β1mRNA in UUO 14 days (r=0.515,0.752 P<0.05).Conclusion:HIF-la may promote the development process of the renal interstitial fibrosis through regulating the expression of CTGF, TGF-β1...