BACKGROUND AND AIMS: Trichostatin A (TSA) is a potent histone deacetylase 
inhibitor and widely used as a promising anticancer agent. Recently, a novel 
insight for TSA has been shown to protect the heart from ischemia/reperfusion 
(I/R) injury in mice, but the underlying mechanism remains unclear. The purpose 
of this study is to investigate whether TSA can influence endoplasmic reticulum 
stress (ERS) and whether its cardioprotective effect is mediated by inhibiting 
myocardial ERS-induced apoptosis in rats.
METHODS: Male Wistar rats were used and pretreated with saline or TSA (0.05, 0.1 
and 0.2 mg·kg(-1)) once daily i.p. for 5 days. I/R model was established by 
occlusion/release of the left anterior descending coronary artery.
RESULTS: TSA significantly reduced myocardial infarct size and plasma activities 
of lactate dehydrogenase and creatine kinase in a dose-dependent manner in rats. 
Accompanied by the reduced injury, TSA also markedly reduced I/R-induced 
myocardial apoptosis (30 min/24 h) by the TUNEL assay. In addition, increased 
expression of glucose-regulated protein 78 (an ERS marker) by Western blot 
showed the effects of TSA on ERS. Induction of C/EBP homologous protein (CHOP), 
a critical mediator for ERS-induced apoptosis, was attenuated by TSA after 
reperfusion for 6 h and 24 h.
CONCLUSIONS: Our findings showed that inhibition of histone deacetylase 
ameliorated I/R-induced myocardial injury in vivo and for the first time 
provided the evidence that suppression of CHOP expression and attenuation of the 
CHOP-induced apoptosis may contribute to the cardioprotection of TSA against 
myocardial I/R injury.