Effect Of Shenmai Injection On Metabonomics Of Heart Failure

Background:Heart failure(HF)is the ultimate destination for the development of various cardiovascular diseases.Ischemic heart disease will eventually evolve into chronic HF on the basis of coronary atherosclerosis.Research on the pathogenesis and intervention strategies around chronic HF is of great significance to improve the level of clinical prevention and treatment.The traditional Chinese medicine Yiqi treatment of HF and the idea of improving cardiac energy metabolism in patients with HF have some common characteristics.Shenmai(SM)and its main component ginsenoside(TSPG)have a good effect on the improvement of cardiac function.Objective:In this study,the molecular level of energy metabolism in cardiomyocytes and the serological indexes of energy metabolism in patients with HF were analyzed.Through the two-part study,the regulatory effect of SM on energy metabolism in HF was comprehensively analyzed.Methods:Part ?: SM improves energy metabolism in patients with HF: a randomized controlled trial In a single-blind,randomized,controlled study,120 patients with HF who met the inclusion and exclusion criteria were divided into three groups:control group(control;Heartfailure HF),Shenmai group(HF+SM)and positive control trimetazidine group(HF+TMZ).The patients in HF group were treated according to the standard treatment guidelines,and the patients in SM group and TMZ group were treated with standard treatment plus corresponding drug therapy for 7 days.The NYHA function grade,TCM-s and BNP level of patients with HF were evaluated before and after treatment.Metabolic substrate detection kit was used to detect the changes of serum free fatty acid(FFA),glucose,pyruvate(PA),branched chain amino acid(branchedchainaminoacids BCAA)and lactic acid(LA)in patients with heart failure before and after treatment.Part ?: the protective mechanism of SM on primary cardiomyocytes I/R through energy metabolism.Primary cardiomyocytes were extracted from neonatal SD rats(24 hours after birth)and divided into 6 groups: normal group(control),ischemia-reperfusion group(Ischemia-Reperfusion I/R),Shenmai group(Ischemia-Reperfusion+Shenmai I/R+SM),levocarnitine group(Ischemia-Reperfusion+L-carnitine I/R+LC),ginsenoside group(Ischemia-Reperfusion+totalsaponinsof Panaxginseng I/R+TSPG)and trimetazidine group(Ischemia-Reperfusion+Trimetazidine I/R+TMZ).The ischemic model was established by glucose-free medium and hypoxia device,and the corresponding drugs were added to each group.The apoptosis of cardiomyocytes,the release activity of lactate dehydrogenase(LDH)and pyruvate kinase(pyruvatekinase PK)in the culture medium,the substrate of energy metabolism and the direct energy supply substance ATP and the energy-producing substrate ADP were detected by related kits.The expression of key enzymes and transporters in the process of myocardial energy metabolism in each group was detected by Western blotting(Westernblot)and reverse transcription-polymerase chain reaction(Reverse Transcription-Polymerase Chain Reaction RT-PCR).Results:There was no significant difference in baseline level among the three groups of patients with HF.After treatment,the functional grade of NYHA in SM group and TMZ group was significantly better than that in control group,and the effect of SM was more significant than that of TMZ(p <0.01).The improvement effect of SM on TCM-s of HF was significantly better than that of control group and TMZ treatment group(P < 0.05).Compared with the control group,SM treatment significantly decreased the level of BNP.In addition,the change ratio of BNP(C-BNP)in SM group and TMZ group was significantly higher than that in control group(p <0.01).After 7 days of treatment,the levels of serum FFA and LA in each group were significantly lower than the baseline level,but there was no significant change in blood glucose level.The levels of uptake and utilization of FFA and PA in SM group were significantly higher than those in TMZ group and control group.In addition,the content of BCAA in SM group increased significantly after 7 days of treatment,and the level of BCAA in SM group was significantly higher than that in TMZ group and control group.SM and its main component TSPG can reduce the injury of cardiomyocytes after I/R and significantly reduce the rate of apoptosis.The release of LDH in SM group was significantly lower than that in TSPG group.The level of competition release in SM group was significantly lower than that in TSPG group.SM could significantly increase the protein expression of key enzymes and transporters of FFA and glucose metabolism pathway in cardiomyocytes treated with I/R.SM significantly increased the uptake of FFA and glucose in the culture medium and decreased the production of LA(P < 0.01).SM could increase the content of ATP and decrease the ratio of ADP/ATP in cardiomyocytes after treatment.Conclusion:SM combined with standard drug therapy can improve cardiac function and clinical symptoms in patients with HF.At the same time,by increasing the intake and utilization of metabolic substrates,improving the energy supply of patients with HF and further improving the quality of life of patients with HF,the effect is more significant than that of positive control TMZ,which proves the clinical value of compound drugs of traditional Chinese medicine in the clinical treatment of HF.SM and its main component TSPG can significantly reduce the injury of cardiomyocytes induced by I/R,improve the utilization of energy substrates,increase the energy production of mitochondrial ATP,correct the disorder of energy metabolism of ADP and ATP in cardiomyocytes,so as to ensure the energy supply of cardiomyocytes and maintain the contractile function of damaged cardiomyocytes.