Effect of metallothionein on the renal injury induced by chronic intermittent hypoxia in mice / 中华肾脏病杂志

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.