Department of Radiation Oncology,Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China (Wu YJ,Wang J,Wang Y,Liu Q,Wang Y,Cao F,Cheng YJ,Jiao WP);Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China (Wang S)
AbstractObjective To study cardioprotective effects of pretreatment with chronic intermittent hypobaric hypoxia (CIHH) on acute radiation-induced heart damage, and to explore the potential mechanisms. Methods Forty-eight male adult Sprague-Dawley rats were randomly divided into control group, CIHH group, radiation group, and CIHH+radiation group. Pretreatment with CIHH was performed by placing rats in a hypobaric chamber before radiation. Left ventricular function was recorded and myocardial infarction area was determined. Collagen volume fraction (CVF) was calculated after Masson staining. The activity of total superoxide dismutase (T-SOD) and content of lipid peroxide malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay. The expression levels of a marker of fibrosis, collagen type I (COL-1), and two markers of endoplasmic reticulum stress, GRP78 and CHOP, were analyzed by Western blot. Difference test using two factor analysis of variance. Results Compared with the radiation group, the CIHH+radiation group had improved left ventricular systolic and diastolic function and reduced myocardial infarction area;the CIHH+radiation group also had significantly reduced CVF, significantly lower expression of COL-1, significantly higher activity of T-SOD, significantly lower concentration of MDA, and significantly lower expression levels of GRP78 and CHOP (P<0.01,P<0.01;(185.19±3.20) vs. (156.61±4.60) U/mgprot, P<0.01;(1.36±0.17) vs. (2.36±0.21) nmol/mgprot, P<0.01;P<0.05;P<0.01). Conclusions Pretreatment with CIHH can to a certain degree reduce radiation-induced damage to the cardiac coronary artery, enhance cardiac tolerance to ischemia/reperfusion injury, reduce myocardial infarction area after ischemia/reperfusion, and improve collagen deposition in perivascular region and myocardial stroma. CIHH protects myocardium probably via inhibition of oxidative stress, endoplasmic reticulum stress, and myocardial fibrosis.