| Objective: Myocardial infarction(MI)is one of the most serious diseases leading to disability and death.Ventricular remodeling after myocardial infarction is the main pathological basis of chronic heart failure.Therefore,how to control ventricular remodeling,protect cardiac function is vital.Studies have shown that hypoxia intervention is beneficial to heart function.This study is aim to observe the effect of Intermittent hypobaric hypoxia(IHH)on cardiac structure,and investigate whether IHH could protect the heart function after MI by up-regulating peroxisome proliferatoractivated receptor ? coactivator 1-alpha(PGC-1?).Method: 24 male adult Sqrague & Dawley(SD)rats were randomly divided into four groups for operation.Sham normoxia intervention group(Sham-Nor,n=6),Sham IHH intervention group(Sham-IHH,n=6),Myocardial infarction normoxia intervention group(MI-Nor,n=6),and MI IHH intervention group(MI-IHH,n=6).The body weight and echocardiography were measured on the 7th day(BASE)and the 35 th day(4W)after surgery.For IHH groups,12 rats were exposed to a hypoxia chamber(simulated altitude: 5000 m,pressure PB=404 mmHg,pressure PO2=84 mmHg)for 4 hours/day(8:00-12:00 am),from the 7th day after surgery until 4 weeks.Normoxia groups were placed under normal atmospheric pressure and oxygen content.All animals were given equal amounts of water and a standard laboratory diet.After 4 weeks of intervention,rats were sacrificed,cardiac index was measured,the proportion of myocardial fibrosis in isolated hearts was detected by MASSON staining,mitochondrial membrane potential was determined by JC-10,and PGC-1a protein expression in myocardium was determined by western blot.Results: 1.By observing the survival status,found that compared with the normoxic intervention group,the IHH intervention group had less activity in the intervention time of 4 hours per day,and the activity outside the intervention time was increased compared with the normoxic intervention group.At the end of 4 weeks' intervention,there was no significant difference in body weight or heart index(heart weight/body weight)between the groups.2.MASSON staining results showed that compared with MI-IHH group,MI-Nor group showed significant ventricular remolding,with thinning anterior wall and a large number of collagen fibers,while MI-IHH group maintained normal morphology without obvious left ventricular remolding.Myocardial fibrosis results showed that the proportion of myocardial fibers of MI-Nor group was greater than MI-IHH group(P<0.001).3.Cardiac ultrasound results showed that after 4 weeks of intervention,LVEDs of MINor group was significantly bigger than MI-IHH group(P<0.01),but FS and LVEF were significantly lower than MI-IHH group(P<0.001,P<0.001).Compared these results with BASE,the LVEDd of Sham-Nor group,MI-Nor and MI-IHH group increased significantly(P<0.05,P<0.001,P<0.05),and the LVEDs of MI-Nor group also increased significantly(P<0.001),the LVEF of MI-IHH group and MI-Nor group increased significantly,(P<0.001,P<0.01),while only the FS of MI-IHH group increased significantly(P<0.001).4.JC-10 results showed that the mitochondrial membrane potential of myocardial cells in Sham-Nor group and MI-IHH group were significantly higher than MI-Nor group,respectively(P<0.001,P<0.001).5.Western-blot results showed that the expression of PGC-1? protein in myocardium of Sham-IHH group and MI-IHH group were significantly higher than Sham-Nor group and MI-Nor group(P<0.05,P<0.05).Conclusion: IHH can promote mitochondrial synthesis and protect mitochondrial function by upregulation of PGC-1? in myocardium,and improve myocardial energy metabolism level reduce myocardial fibrosis and enhance myocardial contractility after MI,thereby improving ventricular remodeling and protecting cardiac function. |
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