Male Wistar rats were used and pretreated with saline or TSA (0.05, 0.1 and 0.2 mg路kg鈭?) once daily i.p. for 5 days. I/R model was established by occlusion/release of the left anterior descending coronary artery.
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.
Our findings showed that inhibition of histone deacetylase ameliorated I/R-induced myocardial injury in聽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.
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