RESUMO
Aim To reveal the aetion mechanism of Trillium tschonoskii Maxim (TTM) in the treatment of myoeardial ischemia ( MI) by using network pharma¬cology combined with molecular docking.Methods Compounds of TTM were detected and fished out from TCMID, TCM@TAIWAN , BATMAN-TCM database, and the literature data from PubMed , CNK1, and WAN- FANGD database.PharmMapper database was used to find the targets related to compounds, and DISGeNET, GeneCards, DrugBank and OMIM databases were used to find the targets related to Ml.The predictive targets of TTM in the treatment of Ml were obtained.Cytosca- ope 3.1.2 Software and String database were used to build compound-target network and PP1 network.Gene ontology ( GO ) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathway enrichment analysis were performed by utili¬zing the CludterProfiler Software package of RStudio software.The molecular docking was used for verifying the results of network analysis.Results The 10 active compounds of TTM were screened , and 13 core targets of Ml were predicted, such as ALB, EGFR, MAPK1 , CASP3,ESR1 ,etc.A total of 28 Ml-related signaling pathways were fished out.The results of molecular docking showed that the core active ingredients had good binding activity with the key targets.Conclusion TTM may play a role in the treatment of Ml through regulating multiple ingredients, multiple pathways, and multiple targets.
RESUMO
Aim To investigate whether hydrogen sul-fide ( H2 S ) inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart. Methods The myocardial ischemia injury model was replicated with Langendorff isolated perfused rat heart, and the left anterior descending coronary ar-tery was ligated for 4 h. 40 male SD rats were divided into five groups randomly: sham group, ischemia group, and NaHS groups (5,10,20μmol·L-1). The segmental heart samples were used for HE staining. Cardiomyocyte apoptosis was detected with TUNEL as-say. The expressions of caspase-3 and Cyt-C in hearts were determined with Western blot analysis. Results Myocardial cells were found to show serious disorder and coagulated zonal necrosis under light microscope, the apoptotic rate of cardiomyocytes and the expression of caspase-3 and Cyt-C were significantly increased af-ter ischemia for 4h. Perfusion of NaHS resulted in more clear cell morphology and milder pathologic chan-ges of myocardiocytes according to the HE staining a-nalysis, and the significant decrease of expression of Cyt-C. After perfusion of 10,20 μmol·L-1 NaHS,the apoptotic rate of cardiomyocytes and the expression of caspase-3 were significantly decreased. Conclusion H2 S has certain protective effects on acute myocardial ischemic injury in isolated perfused rat heart via inhibi-ting cardiomyocyte apoptosis.
RESUMO
Aims To observe the changes of endoge-nous hydrogen sulfide/cystathionine-γ-lyase (H2 S/CSE)system and to study the effects of H2 S on cardiac function,H2 S/CSE and myocardial infarct volumes in acute myocardial ischemic injury in isolated hearts of rats.Methods The myocardial ischemic injury model was established by the ligation of coronary artery.The hemodynamic parameters,such as the left ventricular developed pressure (LVDP),±dp/dtmax and coronary arterial flow(CF),were respectively recorded to evalu-ate the cardiac function.The content of H2 S and the activity of CSE in cardiac tissue were detected respec-tively at each time point after ischemia.Infarct vol-umes in isolated rat hearts were determined by dual staining with Evans-blue and TTC.Results (1 )Com-pared with those of the sham group,LVDP,±dp/dtmax and CF were significantly decreased at 30 min,1,2,3, 4 h after ischemia(P<0.01),there were no statistical-ly significant differences in the content of H2 S and the activity of CSE in cardiac tissue at 3 0 min after ische-mia.But during the periods from 1 h to 4h after ische-mia,the content of H2 S and the activity of CSE in car-diac tissue were significantly decreased,the infarct volumes were greatly increased compared with those of the sham control group (P<0.05 or P<0.01 ).(2) Compared with those of the ischemia 4h group,LVDP, ±dp/dtmax and CF were significantly increased in the NaHS low,middle and high dose groups (P<0.05 or P<0.01),the content of H2S and the activity of CSE in cardiac tissue were significantly increased in the NaHS low,middle and high dose groups(P<0.05 or P<0.01 ),and the infarct volumes were significantly decreased in NaHS middle and high dose groups(P<0.01 ).Conclusion H2S and CSE are involved in myocardial ischemic injury in isolated hearts of rats. Administration of NaHS could enhance the activity of CSE,increase the content of H2 S,and reduce infarct volumes.It could be suggested that H2 S has cardiopro-tective effects on acute myocardial ischemic injury.