Study On The Mechanisms Of The Calcineurin On The Myocardium Apoptosis Induced By Ischemia-reperfusion And Adrenergic Receptors

ChapterⅠEffect of the calcineurin(CaN) on the myocardium apoptosis induced by hypoxia-reoxygenation and adrenergic receptorsObjective To explore the effect of calcineurin on the myocardium apoptosis in vitro induced by hypoxia-reoxygenation(H/R) and adrenergic receptors.Methods Primary neonatal rat cardiomyocytes were generated and cultured, which were disposed with 4 hours of reoxygenation after 24 hours of hypoxia (24H/4R)and (or) isoproterenol(10μM). The levels of calcineurin were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and the rate of the cardiomyocyte apoptosis was assessed by flow cytometry and DNA laddering .Results Isoproterenol(10μM) could promote the rate of cardiomyocyte apoptosis induced by 24H/4R(10.763±1.554 vs 8.737±1.120, P﹤0.05). The mRNA levels of calcineurin were significantly on the rise during the curse of the apoptosis induced by 24H/4R and isoproterenol(0.689±0.035 vs 0.464±0.023, P﹤0.01). CsA (Cyclosporin A), calcineurin inhibitor, can inhibit dramatically the apoptosis induced by 24H/4R and isoproterenol(6.270±0.306 vs 10.763±1.554, P﹤0.01).Conclusionsβ-adrenergic receptor agonist can enhance cardiomyocyte apoptosis induced by 24H/4R. Correspondingly, the levels of calcineurin increases. CsA can attenuate the cardiomyocyte apoptosis induced by 24H/4R and isoproterenol(10μM) .It suggests that calcineurin signaling would stimulate cardiomyocytes apoptosis induced byβ-adrenergic receptor agonist and H/R.ChapterⅡStudy on the effect of calcineurin Aαgene overexpression on the myocardium apoptosis induced by hypoxia-reoxygenation and adrenergic receptorsObjective Adenovirally mediated gene transfer of a constitutively calcineurin AαcDNA (AdCnAα) was performed in cultured neonatal rat cardiomyocytes to elucidate the mechanism whereby calcineurin affected cardiomyocytes apoptosis induced by hypoxia-reoxygenation(H/R)...