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Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.
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Animales , Ratas , Insuficiencia Cardíaca/tratamiento farmacológico , Medicina Tradicional China , Panax , Proteómica , Qi , Ratas Sprague-DawleyRESUMEN
Objective:To explore the mechanism of the prescription consisting Aconiti Lateralis Radix Praeparata and Epimedii Folium in the treatment of chronic heart failure （CHF） based on network pharmacology，followed by verification in H9c2 myocardial cells with hypoxia-reoxygenation injury <italic>in vitro</italic> and in zebrafish with vascular endothelial growth factor receptor （VEGFR） tyrosine kinase inhibitor Ⅱ （VRI） -induced vascular insufficiency. Method:The active ingredients in Aconiti Lateralis Radix Praeparata and Epimedii Folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），the corresponding target genes from the Universal Protein Resource （UniProt）， and the CHF-related targets from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Both the active ingredient-potential target network and the active ingredient-CHF-related target network were generated using Cytoscape 3.6.1， followed by the protein-protein interaction （PPI） network construction and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genome （KEGG） enrichment analysis based on MetaScape. H9c2 myocardial cells exposed to hypoxia-reoxygenation were selected for determining the proliferation-promoting effect by methyl thiazolyl tetrazolium （MTT） assay. The protein expression of B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein（Bax），cysteinyl aspartate-specific protease-3（Caspase-3）， protein kinase B（PKB/Akt），phosphorylated protein kinase B（p-Akt），phosphorylated extracellular signal-regulated kinases 1/2 （p-ERK1/2），extracellular signal-regulated kinase 1/2 （ERK1/2）， and poly adenosine diphosphate ribose polymerase（PARP）was detected by Western blotting. The efficacy of the prescription in promoting angiogenesis was verified in a zebrafish model of VRI-induced vascular injury. Result:There were 28 active ingredients for the prescription， 209 corresponding targets， 1 296 CHF-related targets， and 94 common gene targets shared by the prescription and CHF. PPI network clustering suggested that Aconiti Lateralis Radix Praeparata and Epimedii Folium alleviated CHF by interfering with cell differentiation and metabolism and angiogenesis. GO analysis revealed that CHF relief was achieved via the intervention in such biological processes as cell migration，vascular development， and angiogenesis. Pharmacodynamic experiments verified that Epimedii Folium （10 mg·L<sup>-1</sup>） alone and the prescription （10 mg·L<sup>-1</sup>）both enhanced the proliferation of H9c2 myocardial cells under the hypoxia-reoxygenation condition （<italic>P</italic><0.05），while the latter also increased the expression of Bcl-2，Bcl-2/Bax， and PARP （<italic>P</italic><0.05） and reduced the expression of Caspase-3， Akt， and ERK （<italic>P</italic><0.05）. The prescription at the concentrations of 0.3 and 0.1 g·L<sup>-1</sup> promoted angiogenesis （<italic>P</italic><0.05）. Conclusion:Aconiti Lateralis Radix Praeparata and Epimedii Folium exert the therapeutic effect against CHF via multiple ingredients，multiple targets， and multiple channels. Such combination promotes the proliferation of H9c2 myocardial cells under hypoxic condition and protects zebrafish from vascular injury by up-regulating the expression of Bcl-2 and PARP，increasing Bcl-2/Bax ratio，and down-regulating the expression of Caspase-3，Akt， and ERK.
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Objective To study the efficacy enhancing and toxicity reducing effects of compatibility of Aconitum carmichaeli and Cornus officinalis on chronic heart failure (CHF) rats. Methods The CHF rats was established by ip injection of adriamycin (ADM), the CHF rats were administrated tested drugs for three weeks by means of ig administration, the tested drugs included extracts of A. carmichaeli, C. officinalis, and Compound. The serum brain natriuretic peptide (BNP) level, activity of Ca2+-ATP and Na+, K+-ATP enzymes in cardiac myocytes, and cardiac histopathology were measured. Results After three weeks of modeling, the CHF rats showed signs of ascites, loss of weight, loose stool, hogback, etc. The left ventricular ejection fraction (EF) and fraction shortening (FS) decreased significantly, and the level of BNP in serum was significantly improved; Pathological changes of ventricular tissue included rupture of myocardial fibers, degeneration and necrosis of cardiomyocytes, etc. After three weeks of gavage compatibility of A. carmichaeli and C. officinalis, the general state and cardiac histopathology of the animal was obviously improved, the level of BNP in serum was reduced significantly, the activity of Na+, K+-ATP enzymes was increased significantly. No notable improvement in the above indexes was obtained after administration of A. carmichaeli and C. officinalis alone. Conclusion The compatibility of A. carmichaeli and C. officinalis can increase the activity of Na+, K+-ATP enzyme in cardiac myocytes, and improve the energy metabolism and activity of cardiac myocytes in chronic heart failure. The compatibility of A. carmichaeli and C. officinalis play the key role of enhancing efficacy and reducing toxicity.
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Objective@#To explore the effects of exercise rehabilitation on the depression and anxiety state and quality of life in patients with chronic heart failure.@*Methods@#400 cases of chronic heart failure patients were selected as the research objects.They were randomly divided into control group(n=200)and exercise rehabilitation group(n=200) by random number table.Two groups were given symptomatic treatment and routine care on a regular basis, and exercise rehabilitation group again on this foundation to give rehabilitation therapy for 3 weeks.Self-rating anxiety scale(SAS) and Self-rating depression scale(SDS)were used to score the anxiety and depression of the two groups before and after rehabilitation.The SF-36 was used to assess the quality of life of patients.Rehabilitation satisfaction questionnaire was used to investigate the satisfaction degree of rehabilitation.@*Results@#There was no significant difference in SAS and SDS scores between the two groups before intervention (P>0.05). After intervention, the SAS and SDS scores of the two groups were significantly lower than those before intervention (P<0.05). SAS and SDS scores in exercise rehabilitation group ((27.47±4.82)vs(45.63±5.61))were significantly lower than those in control group ((43.17±4.81) vs (59.61±4.18))(P<0.05). Before intervention, there was no significant difference in the scores of SF-36 scale between the two groups (P>0.05). After intervention, the scores of SF-36 scale were significantly increased in the two groups, and the difference was statistically significant compared with that before intervention (P<0.05). All the factors of SF-36 in exercise rehabilitation group were significantly higher than those in control group (mental health: (72.06±7.48)vs(64.34±7.01), emotional function: (81.06±7.01)vs(76.05±6.92), social function: (81.14±7.83)vs(71.26±7.65), overall health: (70.14±8.05)vs(61.26±7.95), energy: (74.56±7.81)vs(69.46±7.40), the body pain: (68.51±7.36)vs(60.26±7.51), physical limitations: (64.99±7.31)vs(59.62±7.53 ), physiological function: (69.71±7.63)vs(63.84±7.04), all P<0.05). The satisfaction of the exercise rehabilitation group (92.5%)was significantly higher than that of the control group(75.0%) (P<0.05).@*Conclusion@#Exercise rehabilitation training can not only improve the anxiety and depression of patients with chronic heart failure, but also effectively improve the quality of life of patients.Exercise rehabilitation training has a high degree of recognition, and is worthy of extensive application in clinical practice.
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Objective To evaluate the clinical significance of the changes of plasma B-type natriuretic paprid and NT-pro BNP levels in patients with chronic heart failure(CHF).Methods 120 consecutive patients hospitalized for CHF were retrospectively studied.NT-pro BNP and LVEDD,LVESD,LVEF were measured and compared in 120 patients and 50 normal control subjects before medical treatment and on discharge.Results The plasma NT-pro BNP levels in patients with CHF were significantly higher than controls( P <0.05).The plasma NT-pro BNP levels in patients with cardiac function NYHA Ⅰ were significantly higher than controls( P < 0.05).As the cardiac function deteriorated from NYNA Ⅰ to NYNA Ⅳ,the NT-pro BNP levels increased consecutively with significant differences from each other ( P < 0.05).The plasma NT-pro BNP levels was low when CHF was cured ( P < 0.05 ).Conclusion Determination of plasma NT-pro BNP levels in patients with CHF were helpful to study the severity and prognosis of disease.
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Objective To investigate the change of heart rate turbulence in patients with chronic heart failure and relationship to age、LVEF、LVED、heart rate before ventricular premature complex (VPC)、coupling interval、compensatory interval、the number and origin of VPC.Methods HRT was measured in 30 CHF patients and 30 healthy controls.HRT onset and slope were measured by the original definitions using Holter records and compared with the clinical factors.Results The HRT TS was significantly lower in patients wtih heart failure than in control (3.17?2.03vs9.64?6.47,P