RESUMO
Objective::To observe the intervention effect of Yiqi Huoxue recipe (YQHX) on ventricular remodeling in rats with chronic heart failure, in order to explore its mechanism. Method::Among 40 male SD rats, 10 were randomly selected as the sham operation group. The left anterior descending coronary artery ligation was performed to construct the chronic heart failure(CHF) rat model. After modeling, they were randomly divided into model group, captopril group(13.5 mg·kg-1·d-1) and YQHX group (20 g·kg-1·d-1), and orally given the corresponding drugs. After 8 weeks of intervention, cardiac tissues were collected, body mass and heart mass were weighed, and echocardiography were performed to detect the changes in cardiac structure. Masson staining was performed to determine the myocardial interstitial collagen volume fraction. Western blot was used to detect the expression levels of mitochondrial fusion protein optic atrophy 1 (Opa1) and cleavage protein dynamic-related protein 1 (Drpl). The quantitative real-time fluorescence polymerase chain reaction(Real-time PCR)was applied to detect the expressions of Wnt/β-catenin pathway-related factors such as lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase-3β (GSK-3β) and β-catenin. Result::Compared with the sham group, the left ventricular wall of the model group was significantly thickened (P<0.05), the cardiac cavity was significantly enlarged, and the content of collagen in the myocardial interstitium was increased (P<0.01). The expression level of Opal decreased, the expression level of Drp1 increased (P<0.05), the mRNA expression level of LRP6, GSK-3, and β-catenin increased (P<0.01). Compared with the model group, YQHX group can reduce ventricular wall thickening, heart chamber enlargement, myocardial interstitial collagen content, up-regulate the low expression of Opa1, but down-regulate the high expressions of Drpl, LRP6, GSK-3β, β-catenin(P<0.05, P<0.01). Conclusion::YQHX can effectively alleviate ventricular remodeling and improve mitochondrial energy metabolism in rats with CHF. The mechanism may be related to the inhibition of Wnt/β-catenin related factors.
RESUMO
Objective Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Simiao Yongan Decoction for angiogenesis. Methods Chemical components and targets related to the four traditional Chinese medicine (TCM) herbs were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Compound-target network were constructed to explore the mechanism of Simiao Yongan Decoction. Through OMIM database, TTD database, and PharmGkb database, the targets of angiogenesis were selected, and then the network diagram of disease-target interaction was constructed; The nuclear target of drug target and disease target interaction diagram was screened, ClueGO was used to carry out GO analysis of the nuclear target, and KEGG database was used to carry on the related pathway enrichment of the nuclear target. Results Selecting the oral bioavailability (OB) ≥ 30% and drug likeness (DL) ≥ 0.18 as filter condition, 120 active ingredients and 155 corresponding protein targets were screened from Simiao Yongan Decoction. Through the evaluation of network topological characteristics, such as degree, medium degree, and proximity to the center, 197 targets were selected to serve as the nuclear target in atherosclerosis. A total of 942 gene ontology (GO) entries were screened out, including 685 biological process entries, 164 molecular function entries, and 93 cellar component entries. The KEGG database was used for the enrichment of the selected targets, and 20 pathways were screened which had effect on angiogenesis. Conclusion This study revealed the main active compounds and possible mechanism of Simiao Yongan Decoction for treatment of angiogenesis and verified the characteristics of multi-components, multi-targets, and integral regulation for Simiao Yongan Decoction, predicting the main possible mechanism for the treatment of angiogenesis, which provided theoretical basis for the study of active ingredients and experimental research.