Role of peroxisome proliferator-activated receptor alpha activation in acute myocardial damage induced by isoproterenol in rats.
- Author:
Jie YUAN
1
;
Jian WU
;
Zhi-gang HANG
;
Xue-kuan ZHONG
;
Ling-wang ZHOU
;
Bo YU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Creatine Kinase; blood; Energy Metabolism; Fatty Acids, Nonesterified; metabolism; Fenofibrate; pharmacology; Heart; drug effects; Isoproterenol; toxicity; L-Lactate Dehydrogenase; blood; Male; PPAR alpha; physiology; Rats; Rats, Wistar
- From: Chinese Medical Journal 2008;121(16):1569-1573
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDPeroxisome proliferator-activated receptor (PPAR) alpha is one of the subtypes of PPARs. It regulates metabolism of lipid and lipoprotein, as well as glucose homeostasis. In addition, PPARalpha influences cellular proliferation, inflammation, differentiation and apoptosis, which plays a vital role in cardiovascular diseases. The purpose of this study was to investigate the role and mechanisms of PPARa activation in relation to acute myocardial damage induced by isoproterenol in rats.
METHODSThirty male Wister rats were randomly divided into control group, isoproterenol (Iso) injured group and fenofibrate (FF) treatment group. Acute myocardial damage caused by isoproterenol intraperitoneal injection induced ischemia was established. We determined the levels of creatine kinase (CK) and lactic dehydrogenase (LDH) in serum as well as the concentrations of free fatty acids (FFA) in serum and myocardium. The mRNA expressions of PPARa, muscular type carnitine palmitransferase (M-CPT-I) and medium chain lipid acetyl coenzyme A dehydrogenase (MCAD) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTSCompared with the control group, the levels of serum CK and LDH were significantly increased after FF and Iso treatments. Moreover, the concentrations of FFA in both serum and myocardium were obviously increased in the Iso group and FF group, while the mRNA expressions of PPARalpha, M-CPT-I and MCAD declined, respectively (P < 0.01). When compared with the Iso group, significant decreases in serum CK and LDH were observed in the FF group. The concentrations of FFA both in serum and myocardial tissue were markedly decreased in the FF group, while the expressions of PPARalpha, M-CPT-I and MCAD mRNA were increased (vs. Iso, P < or = 0.01).
CONCLUSIONSThe utilization of FFA was reduced in isoproterenol induced acute myocardial damage. PPARalpha activation by its activator fenofibrate may play a key role in energy metabolism in acute myocardial damage induced by isoproterenol in rats.