| Object:In this study,RT-PCR and western blot assays were carried out to investigate the effects of astragalus & semen lepidii on the expression of mitochondrial dynamics-related proteins Drp1 and fission protein Fis1 in failing cardiomyocytes at the level of mitochondrial dynamics by studying a rat model of heart failure.The mechanism and therapeutic effect of astragalus & semen lepidii in the treatment of heart failure cardiomyocytes were determined.At the same time,60 patients with heart failure were randomly selected for clinical efficacy observation.According to the patients’ plasma BNP levels,TCM syndrome scores and quality of life scores,the efficacy of astragalus & semen lepidii in the treatment of heart failure and the improvement of heart failure symptoms were evaluated.This paper was aimed to provide ideas for further research on astragalus &semen lepidii to benefit more patients with heart failure.Methods:1.Animal experimentsFirstly,80 healthy adult male Wistar rats were selected and randomly divided into blank control group(15 rats)and model group(65 rats).After two weeks of normal feeding,rats in the model group were intraperitoneally injected with adriamycin(3mg/kg)for heart failure modeling,while rats in the blank control group were intraperitoneally injected with the same amount of normal saline.Injections were given twice a week and modeling lasted for 4 weeks.At the 4th week after modeling of heart failure,the two groups of rats were examined by doppler echocardiography and plasma BNP,respectively.The left ventricular ejection fraction(LVEF),left ventricular diastolic diameter(LVIDd),left ventricular fractional shortening(LVFS),left ventricular internal dimension systole(LVIDs)and serum BNP were detected to judge whether modeling of heart failure was successful.After heart failure modeling was successful,the rats in the model group were randomly divided into trimetaxine group,astragalus & semen lepidii low-dose group,astragalus &semen lepidii high-dose group,and control group,with 15 rats in each group.Meanwhile,the rats were given drug intragastric administration.Among them,high-dose group-astragalus & semen lepidii 5.4mg/kg,low-dose group-astragalus & semen lepidii2.7mg/kg,trimetazidine group-trimetazidine 10mg/kg,control group-distilled water2ml/rat,qd,and drug intervention lasted for 6 weeks.Plasma BNP and doppler echocardiography were examined again at the second and sixth weeks of intervention and the results were recorded.Later,the experimental animals were killed and their heart tissue was taken.The gene and protein expression of Drp1 and Fis1 were tested by RT-PCR and western blot assays.The statistical data were analyzed and compared.2.Observation of clinical efficacy60 patients with heart failure who met the requirements were randomly selected and divided into control group and experimental group.For the patients in the experimental group,astragalus & semen lepidii were added on the basis of conventional treatment;for the patients in the control group,trimetazidine was added on the basis of conventional treatment.Three months later,the changes of plasma BNP level,cardiac function classification,TCM syndrome score and Minnesota heart failure quality of life score before and after treatment were compared between the two groups of patients.Results:1.Results of animal experimentsAfter the 4th week of modeling,as showed by doppler echocardiography,the LVIDs and LVIDd of the model group were markedly lower than those of the control group,P<0.05.The LVFS and LVEF of the model group were remarkably higher than those of the control group,P<0.05.These findings suggested that the heart failure modeling was successful.LVEF data at week 2 and 6 of intragastrium: high-dose group > trimetazidine group > low-dose group > model group.BNP determination: model group > low-dose group > trimetazidine group > high-dose group.P < 0.05 indicated statistical significance.The results of western blot and RT-PCR assays were as follows.Drp1 m RNA expression level: model group > low-dose group > trimetazidine group > high-dose group > control group.Drp1 protein expression level: model group > low-dose group > trimetazidine group > high-dose group > control group.Fis1 m RNA expression level: model group >low-dose group > trimetazidine group > high-dose group > control group.Fis1 protein expression level: model group > low-dose group > trimetazidine group > high-dose group > control group.Compared with the model group,the m RNA expression levels of Drp1 and Fis1 in the high-dose group,trimetazidine group and low-dose group were relatively decreased,P < 0.01.Compared with trimetazidine group,there were no significant difference in the m RNA expressions of Drp1 and Fis1 between the low-dose group and the high-dose group,P>0.05.Compared with the model group,the protein expressions of Drp1 and Fis1 in the high-dose group,trimetazidine group and low-dose group were decreased,P<0.01.Compared with trimetazidine group,there were no significant difference in the protein expressions of Drp1 and Fis1 between the low-dose group and the high-dose group,P>0.05.2.Results of observation of clinical efficacyAfter treatment,the TCM syndrome scores of the two groups of rats were compared,and it was unveiled that the scores of both groups were declined,and the scores of the experimental group were greater than those of the control group,P=0.005.The comparison of the effective rate of efficacy evaluation displayed that the rate of the experimental group was greater than that of the control group,P=0.264.The comparison between the two groups of plasma BNP unveiled that the plasma BNP of experimental group was greater than that of the control group,P=0.031.After comparing the quality of life scores of the two groups,it was found that the score of the experimental group was greater than the score of the control group,P=0.003.Conclusions:Astragalus & semen lepidii can prominently reduce the plasma BNP of rats with heart failure and improve their cardiac function,and the effect of high dose > the effect of trimetazidine > the effect of low dose.The mechanism of the treatment of heart failure may be related to the down-regulated proteins Drp1 and Fis1.Astragalus & semen lepidii combined with conventional treatment of heart failure can better enhance the curative effect,enhance heart function,and improve the quality of life. |
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