Silencing of hypoxia-inducible factor-1α gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats.

摘要: Overactivation of hypoxia-inducible factor (HIF)-1α is implicated as a pathogenic in chronic kidney diseases (CKD). However, controversy exists regarding the roles HIF-1α CKD. Additionally, although hypoxia and activation are observed various CKD has been shown to stimulate fibrogenic factors, there no direct evidence whether an injurious or protective renal hypoxic injury. The present study determined knocking down gene can attenuate exaggerate damage using ischemic model. Chronic ischemia was induced by unilaterally clamping left artery for 3 wk Sprague-Dawley rats. short hairpin (sh) RNA control vectors were transfected into kidneys. Experimental groups sham+control vector, clip+control clip+HIF-1α shRNA. Enalapril used normalize blood pressure 1 after artery. protein levels remarkably increased clipped kidneys, this increase blocked Morphological examination showed that shRNA significantly attenuated injury kidneys: glomerular indices 0.71 ± 0.04, 2.50 0.12, 1.34 0.11, percentage globally damaged glomeruli 0.02, 34.3 5.0, 6.3 1.6 sham, clip, clip+shRNA groups, respectively. collagen α-smooth muscle actin also dramatically but effect In conclusion, long-term overactivation associated with ischemia/hypoxia.