Effect of metallothionein on the renal injury induced by chronic intermittent hypoxia in mice / 中华肾脏病杂志
Chinese Journal of Nephrology
; (12): 384-388, 2014.
Article
em Zh
| WPRIM
| ID: wpr-447098
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WPRO
ABSTRACT
Objective To investigate the mechanism of chronic intermittent hypoxia (CIH)-induced renal injury and the protection of metallothionein (MT).Methods 8-10 weeks old male MT-1 transgenic (MT-TG) mice (n=12) and the wide type (WT) mice (n=12) were randomly divided into two groups respectively,Air mimic control(Ctrl) group (n=6) and CIH group (n=6).The period of chronic intermittent hypoxia was continued for 8 weeks.The CIH paradigm consisted of 20.9% O2 and 8% O2 fraction of inspiration O2 (FiO2) alternation cycles (30 episodes per hour) with 20 seconds at the nadir FiO2 for 12 hours/day during daylight.The nadir hemoglobin oxygen saturations mainly ranged from 60% to 70%.Urine,blood,kidney were collected at the end of study respectively.Histopathology,Western blotting and colorimetric method for related target were performed respectively.Results In WT mice,renal fibrosis,the expression of connective tissue growth factor (CTGF),type-1 plasminogen activator inhibitor (PAI-1),hypoxia-inducible factor 1α (HIF-1α),transforming growth factor β1 (TGF-β1),phosphorylated Smad2 and the MDA content were significantly increased by CIH (P < 0.01).In WT mice,the expression of MT detected by using Western blotting was significantly decreased by CIH (P < 0.01).However,in MT-TG mice,above-mentioned indicators showed no significant difference between CIH and Ctrl group.Conclusions Oxidative stresses is the main mechanism of CIH-induced renal injury.The possible molecular mechanism of CIH-induced renal injury is that CIH increases the expression of HIF-1α in kidney tissue,then activate the TGF-β1-Smad2 signaling pathway and lead to the renal fibrosis.The protection of MT on CIH-induced renal injury may be via its antioxidant effect.
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Zh
Revista:
Chinese Journal of Nephrology
Ano de publicação:
2014
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Article