Protective Effect Of Astragaloside Ⅳ On Cardiac Hypertrophy In Rats And Its Mechanism

Objective:To investigate the effect of astragaloside IV on cardiac hypertrophy and its regulation on autophagy.Methods:One week after adaptive feeding,fifty male Sprague-Dawley rats were randomly divided into sham operation group and abdominal aortic coarctation group(AAC group).There were 10 rats in sham operation group and 40 rats in the AAC group.In the AAC group,abdominal aortic coarctation was performed.In the sham operation group,the operation procedure was the same as that in the AAC group,but the abdominal aorta was not ligated.One week after the operation,there were 32 rats in AAC group,10 rats in sham group.AAC group was randomly divided into model group,low-dose astragaloside group,high-dose astragaloside group and rapamycin group,8 rats in each group.Rapamycin group was a positive autophagy contrast agent group.They were given the corresponding solvents once a day by gavage for six weeks.At the end of study,three rats were randomly selected from each group,left ventricular mass index(LVW/BW)and cardiac mass index(HW/BW)were measured.HE staining,masson staining and sirius red staining were used to observe the morphological changes of myocardium and the content of hydroxyproline was measured.The expression of LC3II/LC3 I,Beclin1 and AMPK/mTOR signaling pathway proteins were detected by western blot.Results:Compared with the sham operation group,the pathological sections of myocardial tissue in each AAC group showed hypertrophy,disordered arrangement of myocardial cells,deposition of interstitial collagen fibers,significantly increased LVW/BW and HW/BW(P<0.05),significantly increased hydroxyproline content in myocardial tissue(P<0.05),significantly decreased p-AMPK/AMPK,LC3II/LC3 I,Beclin1 protein content(P<0.05),and significantly increased p-mTOR/mTOR(P<0.05).Compared with the model group,the low-dose astragaloside IV group showed that the hypertrophy of cardiomyocytes was relatively light,the gap was roughly equal,the arrangement was relatively neat,LVW/BW and HW/BW were significantly decreased(P<0.05),there was no significant decrease in hydroxyproline content(P>0.05),LC3II/LC3 I and Beclin1 were significantly increased(P<0.05),p-AMPK/AMPK was significantly increased(P<0.05),p-mTOR/mTOR was not significantly decreased(P>0.05).Compared with the model group,the pathological section of high-dose astragaloside IV group showed reduced myocardial hypertrophy,the gap was roughly equal,the arrangement was relatively neat,the deposition of interstitial collagen fibers was reduced,LVW/BW and HW/BW were significantly decreased(P<0.05),the level of hydroxyproline was significantly reduced(P<0.05),autophagy related proteins LC3II/LC3 I,Beclin1 were significantly increased(P<0.05),and p-AMPK/AMPK were significantly increased(P<0.05),p-mTOR/mTOR was significantly decreased(P<0.05).Compared with the model group,the pathological section of myocardial tissue in rapamycin group showed that the hypertrophy of myocardial cells was reduced,the gap was roughly equal,the arrangement was relatively neat,the deposition of interstitial collagen fibers was reduced,LVW/BW and HW/BW were significantly decreased(P<0.05),the level of hydroxyproline was significantly reduced(P<0.05),LC3II/LC3 I,Beclin1 were significantly increased(P<0.05),and p-AMPK/AMPK were significantly increased(P<0.05),p-mTOR/mTOR was decreased significantly(P<0.05).Compared with the low-dose astragaloside group,the high-dose astragaloside group showed that the myocardial hypertrophy was reduced,the gap was roughly equal,the arrangement was relatively neat,the deposition of interstitial collagen fibers was reduced,LVW/BW and HW/BW were significantly decreased(P<0.05),the level of hydroxyproline was significantly reduced(P<0.05),LC3II/LC3 I and Beclin1 were significantly increased(P<0.05),P-AMPK/AMPK increased significantly(P<0.05),p-mTOR/mTOR decreased significantly(P<0.05).Compared with rapamycin group,there was no significant difference in morphology and structure of myocardial cells,LVW/BW decreased(P<0.05),HW/BW had no significant difference(P>0.05),hydroxyproline content decreased significantly(P<0.05),p-AMPK/AMPK protein content had no significant difference(P>0.05),p-mTOR/mTOR protein content decreased(P<0.05),autophagy related protein LC3II/LC3 I and Beclin1 increased in high-dose astragaloside group(P<0.05).Conclusion:1.AAC can successfully construct rat cardiac hypertrophy model.2.As IV has protective effect on cardiac hypertrophy in a dose-dependent manner.3.The protective mechanism of As IV on cardiac hypertrophy may be related to moderately increasing autophagy level and activating AMPK/mTOR signaling pathway to regulate autophagy.