Tilianin inhibits myocardial inflammation and apoptosis in a heart failure model by modulating the SIRT1/NLRP3 inflammasome
XU Fengmei
MA Zhancun
Abstract：Objective To investigate the effects of tilianin(TIL)treatment on the structure and function of rat cardiomyocytes,inflammation and apoptosis,and the underlying mechanism.Methods A heart failure(HF)rat model was constructed by intraperitoneal injection of adriamycin.Rats were randomly divided into control(NC)group,model group,nociceptin(Lcz696)group,TIL group,TIL+nigericin group(TIL+NIG),and TIL+NIG+resveratrol(TIL+NIG+RES)group,with 10 rats in each group.Cardiac function was assessed by echocardiography and measurement of serum levels of creatine kinase MB(CK-MB)and brain natriuretic peptide(BNP),which were markers of myocardial injury.Cardiomyocyte cross-sectional area was assessed by hematoxylin and eosin(H&E)staining.Terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)was used to detect apoptosis.Pro-inflammatory cytokine levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,IL-1β,and IL-18 were detected using enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the protein expressions of silent information regulatory factor 1(SIRT1)/NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome.Results Left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),CK-MB,BNP,cardiomyocyte cross-sectional area,apoptosis rate,IL-6,TNF-α,IL-1β,IL-18,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and C-caspase-1 levels were significantly higher in the HF group compared to the NC group,whereas the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and SIRT1 were significantly lower(P＜0.05).Compared with the HF group,LVEDD,LVESD,CK-MB,BNP,cardiomyocyte cross-sectional area,apoptosis rate,IL-6,TNF-α,IL-1β,IL-18,NLRP3,ASC,and C-caspase-1 levels were significantly lower in the Lcz696 group and the TIL group,while LVEF,LVFS,and SIRT1 were significantly higher(P＜0.05).Rescue experiments showed that the NLRP3 inflammasome activator nigericin was able to abrogate the inhibitory effect of TIL on cardiomyocyte apoptosis and inflammatory response in HF rats to a certain extent,whereas the SIRT1 activator resveratrol was able to reverse the effect of nigericin.Conclusion TIL attenuates cardiomyocyte apoptosis and inflammatory response,and improves myocardial structure and function in HF rats by up-regulating SIRT1 and inhibiting NLRP3 inflammasome.
Keywords：heart failuretilianincardiac functioninflammationapoptosissilent information regulatory factor 1(SIRT1)/NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome
Publication Date：2025-10-26
Online Publishing Date：2025-11-19(First online date of this platform, not the publication date of the document)
Pages：6( 1611-1616 )