Effects Of Salidroside On Myocardial Autophagy-related Proteins Expression In Rats Under High Altitude Hypoxia

Objective: Simulate high-altitude hypoxia environment to establish the animal models,observe the effect of hypoxia on the myocardial pathological morphology,apoptosis and myocardial autophagy.To observe the effect of salidroside on the changes of myocardial morphology and expression of myocardial autophagy-related proteins LC3,Beclin-1 and P62 under high-altitude hypoxia environment.Methods: The male SPF Wistar rats aged 6~8 weeks were randomly divided into blank control group?model group,low?medium and high dose salidroside group.The blank control group was raised in SPF-class laboratory(average altitude 1500m)and given saline i.g every day.The model group,low?medium and high dose salidroside group were housed in a simulated plateau environment animal experiment cabin for 10 days(the experiment cabin is 6500 m above sea level),and was given saline,20,40,60 mg / kg salidroside i.g.daily.Ten days later,the rats were anesthetized to draw blood and blood gas tests was performed immediately.Then the rat heart was harvested,TUNEL was used to observe the degree of myocardial apoptosis.TEM was used to observe the formation of myocardial autophagosomes.WB was used to detect the expression of autophagyrelated proteins LC3? /?,Beclin-1,P62 in rat cardiomyocytes,and HE staining was used to observe the pathological morphology variety.Results: 1.HE staining and apoptosis results of myocardial in each group: at the average altitude of 1500 m,there was no obvious abnormal change in the morphology of rat cardiomyocytes.Compared with the blank control group,edema,atrophy and necrosis were observed in rat cardiomyocytes at simulated altitude of 6500 m under low-oxygen environment.TUNEL showed that the number of positive staining cells increased,and apoptosis formed obviously.Myocardial cell edema,atrophy,and necrosis were improved in the salidroside treatment group,and the improvement was more obvious in the medium and high dose groups.TUNEL showed that the number of positively stained cells in the salidroside treatment group was significantly reduced,and the degree of apoptosis was reduced related to dose.2.Detection results of myocardial autophagosome and autophagy-related protein expression: TEM showed that autophagosomes were formed in the myocardium of each group of rats under hypoxic environment at 6500 m altitude.WB detection showed that compared with the blank control group,the expression of myocardial autophagy-related proteins LC3? /? and Beclin-1 increased,the degradation of P62 was increased and the expression was weakened under the simulated hypoxic environment at 6500 m altitude(P<0.05);After salidroside treatment,the expression levels of autophagy-related proteins LC3?/?,Beclin-1 increased,and the expression of P62 decreased(P<0.05).Compared with different doses of salidroside group,the expressions of autophagy proteins LC3?/? and Beclin-1 increased and the expression of P62 decreased in the middle and high dose groups compared with the low dose group,the difference was statistically significant(P<0.05);However,there was no statistically significant difference in protein expression between the middle and high-dose salidroside groups(P> 0.05).Conclusion: 1.The expression of autophagy-related proteins in rat myocardium could be induced by altitude hypoxia.2.The intervention of salidroside can reduce myocardial cell morphology destruction and reduce myocardial cell apoptosis in high-altitude hypoxia environment.3.The protective effect of salidroside on rat myocardium under altitude hypoxia was related to the up-regulation of autophagy-related protein expression.