OBJECTIVEChronic intermittent hypoxia (CIH) animal model was used to mimic the status of obstructive sleep apnea (OSA) in order to investigate the pathological mechanism of CIH-induced cardiac remodeling and observe the protective effect of antioxidants.

METHODSFVB mice (8-10 weeks-old) were randomly divided into control (saline, i.p.) group and CIH group, reduced form of nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (APO, 3 mg×kg(-1)×d(-1), i.p.) alone or CIH+APO, SOD mimic MnTMPyP (SODM, 5 mg×kg(-1)×d(-1), i.p.) alone or CIH+SODM (n = 5 each). After 4 weeks, cardiac function and structure were determined by echocardiography, cardiac inflammation, apoptosis, cardiac fibrosis and cardiac MDA contents were examined by Western blot and chemical-biological methods, respectively.

RESULTS(1) Heart weight, LVIDd and LVIDs were increased while LVEF and FS were reduced in CIH group compared to control group (all P < 0.05). (2) Myocardial protein expression of ANP and VCAM-1 was significantly upregulated, myocardial MDA content and apoptosis as well as myocardial fibrosis marker CTGF and PAI-1 were increased in CIH group compared to control group (all P < 0.05). (3) Above parameters were similar between APO and CIH+APO as well as SODM and CIH+SODM (all P > 0.05).

CONCLUSIONCIH could induce cardiac remodeling and CIH-induced cardiac inflammation, cardiac oxidative injury, cardiac apoptosis and cardiac fibrosis serve as the pathological mechanisms of CIH-induced cardiac remodeling. The protective effects of the two antioxidants suggest that the main mechanism of CIH-induced cardiac injury is oxidative stress.