Influence of Anthocyanins on Th17/Treg Balance in Autoimmune Myocarditis Rats by Regulating JAK2/STAT3 Signaling Pathway
Objective:To investigate the influences of anthocyanins on T helper-17 cells(Thl7)/regulatory T cell(Treg)balance and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in autoimmune myocarditis(AE)rats.Methods:Sixty SD rats were randomly grouped into control(NC)group,Model group,anthocyanin group(50 mg/kg anthocyanin),STAT3 activator Colivelin group(1 mg/kg Colivelin),anthocyanin+Colivelin group(50 mg/kg anthocyanin+1 mg/kg Colivelin),with 12 rats in each group.Enzyme linked immunosorbent assay(ELISA)was used to detect the level of serum inflammatory factor.Hematoxylin-eosin(HE)staining was applied to detect myocardial pathological changes.Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL)staining was applied to detect cardiomyocyte apoptosis.Real-time quantitative polymerasechain reaction(RT-qPCR)was applied to detect the expression of retinoid-related orphan receptorγt(RORγt)and fork-head box protein(Foxp3)mRNA in spleen.Western Blot was used to detect the expression of JAK2/STAT3 pathway related proteins in the myocardium.Results:In the Model group,myocardial necrosis and edema were obvious,and a large number of inflammatory cells were infiltrated;the myocardium in the anthocyanin group showed no evident necrosis or cell swelling;the myocardial injury was aggravated in the Colivelin group;inflammatory cell infiltration increased in the anthocyanin+Colivelin group.Compared with NC group,the levels of interleukin(IL)-17,IL-23,RORyt mRNA,Th17 cells,ratio of Th17/Treg,cardiomyocyte apoptosis rate,and ratios of p-STAT3/STAT3 and p-JAK2/JAK2 in Model group were greatly increased(P<0.05),the levels of IL-10,IL-4,Treg cells and FoxP3 mRNA were greatly decreased(P<0.05).Compared with the Model group,the levels of IL-17,IL-23,RORγt mRNA,Th17 cells,ratio of Th17/Treg,cardiomyocyte apoptosis rate,and ratios of p-STAT3/STAT3 and p-JAK2/JAK2 in anthocyanin group decreased(P<0.05),the levels of IL-10,IL-4,Treg cells and Foxp3 mRNA increased(P<0.05);the corresponding indicators in the Colivelin group showed the opposite trends(P<0.05).Compared with anthocyanin group,the levels of IL-17,IL-23,RORγt mRNA,Th17 cells,ratio of Th17/Treg,cardiomyocyte apoptosis rate,and ratios of p-STAT3/STAT3 and p-JAK2/JAK2 in anthocyanin+Colivelin group increased(P<0.05),the levels of IL-10,IL-4,Treg cells and Foxp3 mRNA decreased(P<0.05).Conclusion:Anthocyanins may restore the balance of Th17/Treg by inhibiting the JAK2/STAT 3 pathway and achieve the protective effect on the myocardium of AE rats.
autoimmune myocarditisanthocyaninsJanus kinase 2/signal transducer and activator of transcription 3 signaling pathwayT helper-17 cells/regulatory T cell balanceinflammatory responseexperimental study
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维普
