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


CONCLUSIONS
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.
Wang
Chi
C
Department of Clinical Pharmacology, China Medical University, Shengyang 110001, China.
Chang
Tian-Hui
TH
Zhang
Xin-Hua
XH
Wang
Huai-Liang
HL
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002316:Cardiotonic Agents; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C441070:praeruptorin A; D003402:Creatine Kinase