YE Ping1,FANG Hong1,2,ZHOU Xin2,HE Yan-li1,2,LIU Yong-xue3
1.Department of Geriatric Cardiology,Chinese PLA General Hospital,Beijing 100853,China;2.Genter of Genetic Diagnosis,Southcenter Hospital affiliated to Wuhan University,Wuhan 430071,China;3.Institute of Radiation Medicine,Academy of Military Medical Science,PLA,Beijing 100850,China
Abstract��
OBJECTIVE To investigate the effects of peroxisome proliferator-activated receptors (PPARs)--fenofibrate and pioglitazoneon tumor necrosis factor-�� (TNF-��) expression in cardiac myocytes of neonatal rat. The possible mechanism of action was explored. METHODS Primary cultures of cardiac myocytes were prepared from 1 - 3 day old Wistar rats, and then the myocytes were exposed to lipopolysac-charide (LPS) and fenofibrate and pioglitazone at different concentrations. RT-PCR and EL1SA were used to measure TNF-�� expression in cultured cardiac myocytes. Transient transfection of TNF-�� promoter with or without nuclear factor-kappaB (NF-icB) binding site to cardiac myocytes was performed. RESULTS Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNF-�� mRNA and protein expression in dose-dependent manner. Proportional supression of TNF-�� promoter activity was observed when the myocytes were transiently transfected with whole length of TNF-�� promoter ( - 721/ +17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of the promoter activity was observed with the transfection of TNF-�� reporter with deletion of NF-icB binding site ( - 182/ + 17) . CONCLUSION Fenofibrate and pioglitazone inhibit cardiac TNF-a expression and appear to play a role in anti-inflammation. The mechanism may be partly involved in suppression of NF-��B pathway.
YE Ping,
FANG Hong,
ZHOU Xin etc
.Effects of fenofibrate and piogilitazone on tumor necrosis factor-�� exprssion in neonatal rat cardiac myocytes [J] Chinese Pharmaceutical Journal, 2004,V40(04): 258-260
2004, Vol. 40 