Effect of hyperbaric oxygen therapy on myocardial fibrosis and expression of oxidative stress-related indicators in D-galactose-induced senescent model mice / 中华老年医学杂志

ABSTRACT

Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.