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Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat ment of myocardial ischemia-reperfusion injury ( MI-RI) via using network pharmacology approach, molecu¬lar docking techniques and experimental studies. Methods The active ingredients and targets of Gin¬seng-Rhodiola rosea were screened through the TCMSP database and literature supplementation, and the GEN-EC ARDS ,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI. Functional pro¬tein interaction networks (PPIs) and the STRING database were used to screen out core targets. The DAVID database was also selected for gene ontology functional analysis ( GO) and KEGG signaling pathway enrich¬ment analysis. Lastly, the preliminary validation was performed with the help of molecular docking techniques and experimental studies. Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained, and targets such as IL-6 , TNF-α and VEGFA were found to be closely related to MIRI, mainly involving TNF, PDK-Akt, HIF-1 and other signaling pathways.The molecular docking results showed that soysterol, ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6, TNF-α,Caspase-3,VEGFA,MAPK1 and other targets, among which the best binding was between Caspase-3 and ginsenoside rh2. The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion , reduce myocardial cell edema and vascular congestion, and decrease the expression levels of TNF-α and IL-6 in MIRI rats. Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α, Caspase-3, VEGFA and MAPK1 through dousterol, ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress, reduce cardiomyocyte damage and exert therapeutic effects on MIRI.
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Aim Timely re establishment of coronary blood How in patients with myocardial infarction is the cornerstone of their treatment; however, substantial amount of damage can oecur as a consequence of reperfusion.In recent years it has been found that receptor interacting protein kinase 3 ( RIPK3 ) contributes remarkably to myocardial ischemia-reperfusion injury (MIRI).RIPK3 can regulate necroptosis through RIPK1/RIPK3/MLKL and CaMKII, respectively, and participate in the MIRI process.This artiele reviews the researeh progress of RIPK3-mediated ne¬ croptosis involved in MIRI from endoplasmic reticulum stress, mitochondrial fragmentation disturbanee, cardiac microvascular dysfunction and inflammation, and focuses on whether RIPK3 can be used as a new target for anti-MIRI, so as to provide a new strategy and choice for improving the clinical treatment effect and prognosis of ischemic heart disease.
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OBJECTIVE@#To compare the effects of electroacupuncture (EA) at different time during reperfusion on the expression of autophagy-related protein Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the autophagy-related mechanism of EA on protecting MIRI.@*METHODS@#A total of 72 SD rats were randomly divided into a sham operation group, a model group, a RA group, a RB group, a RC group and a RD group, 12 rats in each group. Except the sham operation group, the rats in the remaining groups were treated with ligating the left anterior descending artery (LAD) for 30 minutes followed by reperfusion to establish the model of MIRI. The rats in the sham operation group were treated with crossing a line through the LAD. The rats in the model group did not receive treatment. The rats in the RA group, RB group, RC group and RD group were treated with EA at "Neiguan" (PC 6) for 20 min, starting at 0 h, 0.5 h, 1 h, 2 h after reperfusion. Evans Blue-TTC double-staining was employed to evaluate myocardial infarct size; the serum CK-MB was detected by ELISA and the expression of Bcl-2 and Beclin1 protein in myocardial tissue were detected by Western blot.@*RESULTS@#Compared with the model group, the percentage of myocardial infarct size in the RB group, RC group and RD group was decreased significantly (all 0.05); the increasing of Bcl-2 in the RB group was more significant than that in RC group (0.05).@*CONCLUSION@#EA at different time during reperfusion could reduce myocardial infarct size in rats with MIRI, and EA at 0.5 h after reperfusion has best efficacy; this protective effect may be achieved by increasing Bcl-2 expression and reducing Beclin1 expression to inhibit overautophagy during reperfusion.