Inhibitory effect of intragastric administration of astaxanthin on pressure overload-induced left ventricular hypertrophy in mice and its mechanism
Objective To investigate the inhibitory effects of astaxanthin(AST)on pressure overload-induced left ventricular hypertrophy in mice and to explore its molecular mechanism.Methods Twenty-four C57BL/6 wild-type male mice were randomly divided into the following four groups:sham group,sham+AST group,cardiac hypertrophy group,and cardiac hypertrophy+AST group,with 6 in each group.The model of left ventricular myocardial hypertrophy was established by thoracic aorta coarctation(TAC)in the cardiac hypertrophy group and cardiac hypertrophy+AST group.The thoracic aortas of mice in both the sham group and sham+AST group were not ligated.AST[150 mg/(kg·d)]was intragastrically administered daily from the next day after surgery for 4 weeks in sham+AST group and cardiac hyper-trophy+AST group.The mice in sham group and cardiac hypertrophy group were given the same volume of normal saline.After sacrifice,the ratios of heart weight/body weight(HW/BW)and heart weight/tibia length(HW/TL)of mice were measured.The hypertrophy and fibrosis degree of myocardium in mice were observed by HE staining and Picro Sirius Red(PSR)staining,and the cardiomyocyte cross-sectional area and collagen volume fraction were calculated.The mRNA ex-pression levels of atrial natriuretic peptide(ANP),myocardial β isoform(β-MHC),fibrosis-related molecules collagen fi-ber type Ⅰ(Collα1),and connective tissue growth factor(CTGF)were detected by real-time PCR(RT-PCR).The activi-ty of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in myocardium were estimated by hydroxyl-amine method and thiobarbituric acid method,respectively.The protein expression levels of nuclear factor erythroid-de-rived 2-like 2(Nrf2)and Heme oxygenase 1(HO-1)were detected by Western blotting.Results The myocardial struc-tures in the sham group and sham+AST group were neatly arranged without fibrosis.In contrast,the heart volume and fi-brosis significantly increased in the cardiac hypertrophy group and cardiac hypertrophy+AST group,and the changes in the cardiac hypertrophy group were more obvious.Compared with the sham group and sham+AST group,the HW/BW,HW/TL,cardiomyocyte cross-sectional area and collagen volume fraction increased in the cardiac hypertrophy group and cardiac hypertrophy+AST group,the mRNA expression levels of ANP,β-MHC,Collα1 and CTGF,and myocardial MDA expression increased,while the protein expression levels of Nrf2 and HO-1,and SOD activity decreased,and the changes in the cardiac hypertrophy group were more significant(all P<0.05).Conclusion AST effectively attenuates pressure overload-induced induced left ventricular hypertrophy in mice and its mechanism may be related to reducing the oxidative stress of myocardial tissues by activating Nrf2/HO-1 signaling pathway.
万方数据
维普
