RESUMEN
Background: Nephrotic syndrome (NS) and its numerous complications remain the leading causes of morbidity and mortality globally. Sanqi Qushi granule (SQG) is clinically effective in NS. However, its potential mechanisms have yet to be elucidated. Methods: A network pharmacology approach was employed in this study. Based on oral bioavailability and drug-likeness, potential active ingredients were picked out. After acquiring overlapping targets for drug genes and disease-related genes, a component-target-disease network and protein-protein interaction analysis (PPI) were constructed using Cytoscape, followed by GO and KEGG enrichment analyses. Adriamycin was injected into adult male Sprague-Dawley (SD) rats via the tail vein to establish NS model. Kidney histology, 24-hr urinary protein level, creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) level were assessed. Western blotting, immunohistochemistry, and TUNEL staining were applied. Results: In total, 144 latent targets in SQG acting on NS were screened by a network pharmacology study, containing AKT, Bax, and Bcl-2. KEGG enrichment analysis suggested that PI3K/AKT pathway was enriched primarily. In vivo validation results revealed that SQG intervention ameliorated urine protein level and podocyte lesions in the NS model. Moreover, SQG therapy significantly inhibited renal cells apoptosis and decreased the ratio of Bax/Bcl-2 protein expression. Moreover, we found that Caspase-3 regulated the PI3K/AKT pathway in NS rats, which mediated the anti-apoptosis effect. Conclusion: By combining network pharmacology with experimental verification in vivo, this work confirmed the treatment efficacy of SQG for NS. SQG protected podocyte from injury and inhibited kidney apoptosis in NS rats via the PI3K/AKT pathway at least partially.
Asunto(s)
Medicamentos Herbarios Chinos , Síndrome Nefrótico , Podocitos , Masculino , Ratas , Animales , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Proteína X Asociada a bcl-2 , Ratas Sprague-Dawley , Proteinuria , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
The evolution from "vessel dominated by heart" of "heart dominating pericardium meridian of hand-jueyin" was sorted out. It was the process in which the heart concept was understood from two aspects rather than from one. The statement, "heart dominating pericardium meridian of hand-jueyin" is originated from Chapter Ten of Lingshu (The Spiritual Pivot). But such pericardium meridian has not be mentioned in the early bamboo slip and silk, i.e. Zubi Shiyimai Jiujing (Moxibustion Classics of Eleven Meridians of Legs and Arms) and Yinyang Shiyimai Jiujing (Moxibustion Classic on Eleven Yin and Yang Meridians). "Twelve meridians" unearthed from Laoguanshan is named as the trajectory of "vessel dominated by heart", which was originally recorded for the diseases of heart system. In later evolution, in order to match three hand yin meridians with two organs in the upper jiao, the ancient physicians proposed the theory as heart dominating meridian, "enveloping heart system" "heart being not be attacked by pathogens" and "pathogen attacking the vessel covered around heart" along with following the records of "twelve meridians" unearthed from Laoguanshan, i.e heart dominating heart system and hand-shaoyin entering heart. Hence, it stands to reason that heart matches with shaoyin and the acupoints are selected from the meridian dominated by heart. In this evolution process, "pericardium" is generated and becomes the third organ in the upper jiao, thus the meridian dominated by heart is named as "hand-jueyin meridian".