Experimental Study on the Improvement of Myocardial Injury in Cardiopulmonary Resuscitation Rats by Total Flavonoids of Scutellaria Barbata Inhibiting Necroptosis Mediated by the TNFR/RIPK Signaling Pathway
Objective:To investigate the effect of total flavonoids of Scutellaria barbata(SBF)on myocardial in-jury in cardiopulmonary resuscitation rats by modulating necroptosis mediated by the tumor necrosis factor recep-tor(TNFR)/receptor-interacting serine/threonine-protein kinase(RIPK)signaling pathway.Methods:A rat mod-el of cardiac arrest/cardiopulmonary resuscitation was established.Successfully modeled rats were randomly divid-ed into four groups:model group,SBF group,specific inhibitor of programmed necrosis-1(Nec-1)group,and SBF+Nec-1 group,with 16 rats in each group.Another 16 rats were taken as the sham operation group.Each group received corresponding drug interventions once daily for 7 days.The levels of left ventricular systolic pres-sure(LVSP),heart rate(HR),and mean arterial pressure(MAP)were measured using a cardiac function detector.Serum lactate(LA)was detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin staining,ni-tro blue tetrazolium chloride staining,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining were used to examine myocardial tissue pathology,myocardial infarction area,and myocardial cell apopto-sis,respectively.Protein expression related to the TNFR/RIPK pathway in myocardial tissue was detected by west-ern blotting.Results:Compared with the sham operation group,the model group showed disordered myocardial cell structure,interstitial edema,partial nuclear condensation,significant decreases in LVSP,HR,and MAP,and significant increases in LA,myocardial infarction area ratio,myocardial cell apoptosis rate,and protein expression of TNFR1,RIPK1,and RIPK3(P＜0.05).Compared with the model group,the SBF group and the Nec-1 group showed reduced myocardial cell structural damage and interstitial edema,significant increases in LVSP,HR,and MAP,and significant decreases in LA,myocardial infarction area ratio,myocardial cell apoptosis rate,and protein expression of TNFR1,RIPK1,and RIPK3(P＜0.05).Compared with the SBF group and the Nec-1 group,the SBF+Nec-1 group showed further improvements in myocardial tissue pathology and the aforementioned quantitative indi-cators(P＜0.05).Conclusion:SBF may improve myocardial function,LA secretion,myocardial tissue pathological injury,and myocardial infarction status in cardiopulmonary resuscitation rats by inhibiting necroptosis mediated by the TNFR/RIPK signaling pathway.
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