| Purpose: 1.To evaluate the effectiveness and safety of Luhong Recipe on patients with yang deficiency and blood stasis syndrome after PCI of ST elevation myocardial infarction through clinical trial.2.Using network pharmacology to predict the potential target and mechanism of Luhong Recipe on myocardial infarction.3.Verifying the main mechanism of Luhong Recipe on myocardial infarction through animal experiments.Methods: Clinical trial: A randomized,double-blind,placebo-controlled clinical trial was used to collect 96 patients with Yang-deficiency and blood syndrome after STEMI PCI,and the patients were randomly divided into treatment group and control group,with 48 cases in each group.The treatment group was given "basic treatment + Luhong Recipe ",and the control group was given "basic treatment + placebo" for 12 weeks.Observing the changes of myocardial enzymes(CK,CK-MB,LDH,TNI)in the two groups of patients at 0 days,3 days,and 7 days;and take 0 weeks and 12 weeks as the observation time nodes to observe the two groups’ heart functional indicators(LVEF,FS,LVEDV,LVESV),BNP,TCM syndromes(scores for main symptoms,scores for minor symptoms,total scores of TCM syndromes,efficacy of TCM syndromes,scores for each symptom),SAQ score(restricted activity score),Angina pectoris frequency score,quality of life score),laboratory indicators(blood lipids,liver and kidney function,electrolytes)and adverse drug reactions,and following up the main adverse cardiac events of the two groups of patients in 24 weeks.Network pharmacology: Obtaining the targets of Luhong Recipe through TCMSP and TCMMESH platforms;obtaining the targets related to myocardial infarction through Gene Cards,Dis Ge NET and OMIM databases;analyzing the main active ingredients of Luhong Recipe through the drug-disease-target network diagram;Using the STRING database to construct the PPI network of the drug and disease intersection targets,and screen out the key targets;using the MCODE plug-in in Cytoscape to screen the main protein functional modules of the intersection target;finally using the DAVID database to perform GO and KEGG enrichment of the main protein functional modules,and predicting the potential mechanism of Lu Hong Recipe.Animal experiment: 75 C57BL/6 mice were randomly divided into control group,myocardial infarction group,LHF-H group,LHF-M group,LHF-L group,15 mice in each group.The drug was given on the day the model was completed.The control group and the myocardial infarction group were given the same amount of normal saline,the LHFH group was given a high-dose Luhong Recipe(15.76g/kg/d),and the LHF-M group was given a medium-dose Luhong Recipe(7.88g/kg/d).The LHF-L group was given lowdose Luhong Recipe(3.94g/kg/d).After 1 week,Evans Blue+TTC staining was used to detect the area of myocardial infarction;4 weeks later,cardiac function indexes(LVEF,FS,LVEDD,LVESD)were detected by echocardiography;pathological structure was observed by HE staining;serum VEGF and HGF were detected by ELISA;PCR and WB detects the PI3K/AKT pathway;immunohistochemistry detects the expression of CD31 and α-SMA;immunofluorescence detects the number of microvessels.Results: Clinical trial: After treatment,the LVEF and FS of the treatment group increased,and both LVEDV and LVESV decreased.The LVEF of the treatment group was higher than that of the control group(P<0.05),and LVEDV was lower than the control group(P<0.05).After treatment,the BNP of the two groups of patients decreased,and the treatment group was lower than the control group(P<0.05).The total effective rate of TCM syndromes in the treatment group was 81.39%,and that in the control group was60.97%.The treatment group was better than the control group.Among them,the treatment group was better than the control group in improving the six symptoms of chest pain,fatigue,cold limbs,backaches and knees,edema of face and limbs,and dark lips(P<0.05).After treatment,the activity restriction score,angina frequency score,quality of life score and total SAQ score of the treatment group increased,and were higher than those of the control group(P<0.05).The incidence of cardiac insufficiency events within24 weeks of the treatment group showed a decreasing trend.During the test,no abnormal laboratory index changes and symptoms and signs of adverse drug reactions were found related to the test drug.Network pharmacology: 444 targets of Luhong Recipe,897 targets related to myocardial infarction and 147 targets of the intersection of the two were obtained through the relevant data platform.Quercetin,progesterone,17-β-estradiol,luteolin and kaempferol may be the main active ingredients of Luhong Recipe.Angiogenesis,cell proliferation,and positive regulation of cell division are the main potential mechanisms of Lu Hong Recipe on myocardial infarction;PI3K/Akt signaling pathway and Fox O signaling pathway are the main potential pathways of Luhong Recipe on myocardial infarction.Animal experiment: Compared with the myocardial infarction group,the myocardial infarction area of each group of Luhong Recipe was reduced(P<0.05).Compared with the myocardial infarction group,the LVEF and FS of each group of Luhong Recipe were increased(P<0.05),and LVESD was reduced(P<0.05),and the LVEF of the mediumdose and high-dose group of Luhong Recipe was higher than the low-dose group(P<0.05),LVESD was lower than the low-dose group.Compared with myocardial infarction group,the myocardial damage of the mice in each group of Luhong Recipe was reduced,the infiltration of inflammatory cells was reduced,the fibrous proliferation was dense,and the ventricular wall thickened;and the damage of the medium-dose and high-dose group of Luhong Recipe was lighter than lower dose group.Compared with the myocardial infarction group,the VEGF and HGF of the Luhong Recipe group were increased(P<0.05),and the HGF of the medium-dose and high-dose group of Luhong Recipe was higher than that of the low-dose group(P<0.05).Compared with the myocardial infarction group,the m RNA expression of PI3 K and Akt in the Luhong Recipe group increased(P<0.05),and the medium-dose and high-dose group of Luhong Recipe was higher than that of the low-dose group(P<0.05).Compared with the myocardial infarction group,the protein expression of PI3 K,P-Akt and Akt in the Luhong Recipe group increased(P<0.05),and the Akt protein expression in the medium-dose and high-dose group of Luhong Recipe was higher than that of the low-dose group(P<0.05).Compared with the myocardial infarction group,the expression of CD31 and α-SMA in the Luhong Recipe group increased(P<0.05),and the expression of α-SMA in the medium-dose and high-dose group of Luhong Recipe was more than that in the low-dose group(P<0.05).Compared with the myocardial infarction group,the number of microvessels in the Luhong Recipe group increased(P<0.05);and the number of microvessels in the medium-dose and high-dose group of Luhong Recipe was higher than that in the low-dose group(P<0.05).Conclusion: 1.Luhong Recipe can optimize the ventricular remodeling of patients after STEMI PCI,improve TCM symptoms and clinical symptoms of patients with Yangdeficiency and blood stasis syndrome after PCI,improve patients’ cardiac function and quality of life,and reduce Heart failure events occurs,the efficacy is safe and accurate.2.Luhong Recipe has a "multi-component-multi-target" network effect on myocardial infarction;its biological effects are mainly enriched in the positive regulation of angiogenesis,cell proliferation,and cell division;the pathways are mainly enriched in the PI3K/Akt pathway And Fox O pathway.3.Luhong Recipe can reduce myocardial infarction area and improve heart function in mice with myocardial infarction,and the medium-dose and high-dose group of Luhong Recipe is better than the low-dose group;its mechanism may be to promote the release of VEGF and HGF and up-regulate the PI3K/Akt pathway,Promote the proliferation of endothelial cells,and then promote microangiogenesis in mice with myocardial infarction,protect the damaged myocardium,and improve heart function. |
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