Netzwerkpharmakologie und experimentelle In-vitro-Verifikation decken den Mechanismus von Hirudin bei der Unterdrückung der Myokardhypertrophie auf

Background: Myocardial hypertrophy is a complex pathological process, which is a common manifestation during the development of various cardiovascular diseases. Hirudin has been shown to have therapeutic effects on a variety of cardiovascular diseases, however, its therapeutic effect on myocardial hypertrophy is still unknown, and its chemical and pharmacological characteristics remain to be elucidated. Methods: In this study, the network pharmacology method was used to characterize the mechanism of hirudin on myocardial hypertrophy. The potential protein targets of hirudin and myocardial hypertrophy were both obtained from the Genecards database, and potential pathways associated with genes were identified by Gene Ontology and pathway enrichment analysis, and the data were displayed in a visual manner. Subsequently, the potential mechanism of action of hirudin on myocardial hypertrophy predicted by network pharmacology analysis was verified by molecular docking, and finally, the main findings were further verified by in vitro experiments by molecular biology techniques. Based on the results obtained from the study of H9c2 cell line, the inhibitory effect of hirudin on myocardial hypertrophy was further proved in the primary rat cardiomyocytes. Results: A total of 250 targets of hirudin, and 5,376 targets related to myocardial hypertrophy after deduplication were collected. The drug-disease network showed the relationship between hirudin, myocardial hypertrophy, and the targets. Further, systematic analysis from the PPI network indicated that blood coagulation, vesicle lumen, and signaling receptor activator activity may be the potential mechanisms of hirudin in the treatment of myocardial hypertrophy, and the PI3K/AKT signaling pathway may be the most relevant to the therapeutic effect of hirudin. Then, three therapeutic targets that were highly related to myocardial hypertrophy were extracted. Hirudin can be highly bound to STAT3, IL-6, and MAPK1 and found by molecular docking, which may be the basis for its inhibitory effect on myocardial hypertrophy. In addition, in vitro experiments showed that hirudin could inhibit AngII-induced hypertrophy and death of H9c2 cells, and significantly reduce the mRNA and protein expression levels of STAT3, MAPK1, and IL-6. The above conclusions were verified in primary rat cardiomyocytes. Conclusion: Hirudin can be used to treat myocardial hypertrophy through a complex mechanism. The application of network pharmacology and experimental validation can promote the application of hirudin in cardiovascular diseases and the interpretation and understanding of molecular biological mechanisms.

Abstract aus PubMed (NCBI) für den zitierten Eintrag, in der Originalsprache wiedergegeben. Maßgeblich ist die Fassung der Originalpublikation.

Das Abstract wird nicht übersetzt, damit die eigene Wortwahl der Autoren erhalten bleibt.

Netzwerkpharmakologie, molekulares Docking und In-vitro-Experimente an H9c2-Zellen und primären Rattenkardiomyozyten dienten der Analyse der Hirudin-Wirkung bei myokardialer Hypertrophie. Nach Deduplizierung fanden sich 250 Hirudin-Ziele und 5 376 Ziele der myokardialen Hypertrophie; die PI3K/AKT-Signaltransduktion erschien am relevantesten. Hirudin band stark an STAT3, IL-6 und MAPK1, hemmte die AngII-induzierte Hypertrophie und das Absterben von H9c2-Zellen und senkte die mRNA- und Proteinexpression von STAT3, MAPK1 und IL-6 signifikant. Laut Autoren kann Hirudin über einen komplexen Mechanismus die myokardiale Hypertrophie behandeln.

Erfahren Sie, wie diese Forschung mit der klinischen Praxis verknüpft ist

Weitere begutachtete Studien in der Kategorie „Arzneimittelentwicklung“.

• Hirudotherapie in Medizin und Zahnmedizin — Jha K et al. (2015)
• Blutegeltherapie: eine Geschichte — Hyson J (2005)
• Hirudine der asiatischen medizinischen Blutegelart Hirudinaria manillensis: gleich und doch verschieden — Lukas P et al. (2019)
• Transcriptomic analysis of the salivary gland of medicinal leech Hirudo nipponia — Lu Z et al. (2018)
• Molekulardynamische und pharmakologische Untersuchungen an durch Protein-Engineering erzeugten Hirudin-Varianten von Hirudinaria manillensis und Hirudo medicinalis — Sun Y et al. (2022)
• Zellfreie Synthese der Hirudin-Variante 1 des blutsaugenden Egels Hirudo medicinalis — Wüstenhagen D et al. (2020)
• Produktion von Hirudin-Varianten durch gentechnisch veränderte mikrobielle Zellfabriken — Zhang J, Lan N (2018)
• Hirudin bei heparininduzierter Thrombozytopenie — Lubenow N, Greinacher A (2002)
• Hirudin verbessert die diabetische Nephropathie durch Hemmung der Gsdmd-vermittelten Pyroptose — Han J et al. (2023)
• Hirudin als alternatives Antikoagulans – eine historische Übersicht — Markwardt F (2002)

Alle von der ASH analysierten Studien →