Effect of metallothionein on the renal injury induced by chronic intermittent hypoxia in mice
10.3760/cma.j.issn.1001-7097.2014.05.011
- VernacularTitle:金属硫蛋白对慢性间断缺氧所致肾脏损伤的保护作用
- Author:
Weixia SUN
;
Xia YIN
;
Yaowen FU
;
Zhonggao XU
- Publication Type:Journal Article
- Keywords:
Reperfusion injury;
Metallothionein;
Oxidative stress;
Hypoxia-inducible factor 1,alpha subunit;
Chronic intermittent hypoxia
- From:
Chinese Journal of Nephrology
2014;30(5):384-388
- CountryChina
- Language:Chinese
-
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.
