| Objectives In this experiment,the effects of Qishen granule on Ang Ⅱ,LDH,heart failure index,heart structure,gastrocnemius structure and strength,PI3K/AKT signaling pathway and atrophy related protein were observed by establishing an animal model of chronic heart failure combined with skeletal muscle atrophy.The purpose of this study was to investigate the mechanism of Qishen granule inhibiting skeletal muscle protein catabolism,and provide evidence for its prevention and treatment of chronic heart failure combined with skeletal muscle atrophy.Methods Eighty male SD rats weighing between 190 and 210 g were randomly divided into modeling group(60)and sham operation group(20)based on weight measurement.After thoracotomy,all rats were subjected to high threading of the anterior descending branch of the left coronary artery.Modeling rats were subjected to high threading and ligation,while rats in the sham group,as control,were subjected to high threading but not ligation.Six to eight pathological Q waves in 12 leads of ECG were selected as screening criteria.Fourtyeight rats with successful modeling and survival were divided into three groups: Model group,Qishen Granule group and Fosinopil group,and the intervention lasted for 12 weeks.During the experiment,the general state of rats such as body weight and hair color was observed.The grip strength of the rats was measured by a tension tester.After the intervention,cardiac LVEF was measured by ultrasound,abdominal aortic blood was collected,and myocardial and gastrocnemius tissues were collected for the following tests:The contents of Ang Ⅱ,NT-pro BNP and LDH were detected by ELISA kit.After HE staining,the myocardial structure and the atrophy of gastrocnemius muscle fibers in each group were observed under microscope,and the cross-sectional area of muscle fibers was calculated by image analysis software.Western Blot was used to detect the expression of atrophy related proteins and PI3K/AKT signaling pathway protein in rat gastrocnemius muscle.Results 1 Compared with Sham operation group,rats in the model group showed the following symptoms: Fur color of the rats was withered.The rats were irritable,and their body weight decreased.Cardiac LVEF of rats decreased significantly,while the concentrations of NT-pro BNP,Ang Ⅱ and LDH increased.HE staining showed that the arrangement of myocardial tissue was irregular.Rat grasp strength,gastrocnemius muscle weight and muscle fiber cross-cross area decreased significantly.Expressions of PI3 K and AKT were reduced,while the expressions of atrophic proteins MAFbx,Mu RF-1 and FOXO1 were significantly increased.2 Compared with Model group,rats in Qisen Granule group and Fosinopil group showed the following symptoms: Fur color of the rats was shiny.Irritability and body weight of rats were improved.Both of Qishen Granule and Fosinopil could improve the rat heart LVEF,reduce the concentrations of NT-pro BNP,Ang Ⅱ and LDH.Rat grasp strength,gastrocnemius muscle weight and muscle fiber cross-cross area increased significantly.Expressions of PI3 K and AKT were elevated(P < 0.05,P <0.01),while the expressions of atrophic proteins MAFbx,Mu RF-1 and FOXO1 were significantly reduced(P < 0.05,P < 0.01).Conclusions 1 Qishen granule can not only improve cardiac function but also inhibit skeletal muscle atrophy.2 The prevention and treatment effect of Qishen granule on chronic heart failure combined with skeletal muscle atrophy may be related to up-regulating the expression of AKT/PI3 K pathway and inhibiting the corresponding muscular atrophy proteins.Figure 7,Table 5;Reference 120. |
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