Effects of dl-praeruptorin A on nucleus factor-kappaB and tumor necrosis factor-alpha expression in ischemia-reperfusion hearts.

Aim: To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression in ischemia-reperfusion (I/R) myocardium.

Methods: Langendorff's isolated rat heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF-kappaB activity in nucleus was analyzed by Sandwich Enzyme-Linked Immunosorbent Assay (ELISA). TNF-alpha level in cytoplasm was measured by radioimmunoassay. Infiltration of neutrophils was observed using Hematoxylin-Eosin staining under optical microscope.

Results: Pd-Ia 1.0 micromol/L with 30-min preventive perfusion decreased NF-kappaB activity from 0.98+/-0.13 to 0.65+/-0.17 (P<0.05 vs solvent) and down-regulated TNF-alpha expression from 13.7+/-6.1 microg/L to 9.4+/-2.7 microg/L (P<0.01 vs solvent) under conditions with increase of coronary flow, negative inotropic action, inhibition of creatine kinase and without chronotropic action, whereas, infiltration of neutrophils was mild.

Conclusion: Pd-Ia inhibited NF-kappaB activativity in I/R myocardium and led to down-regulation of TNF-alpha expression, which might be one of molecular mechanisms of Pd-Ia in cardioprotection.