Experimental study on the effects of granulocyte colony stimulating factor on myocardial apoptosis following coronary microembolization / 中华老年医学杂志

ABSTRACT

ObjectiveTo investigate the effects of granuloeyte colony stimulating factor (G-CSF) on myocardial apoptosis and left ventricular function following coronary mieroembolization (CME).MethodsA total of 68 male Sprague Dawley rats were randomized into control group(n=24), G-CSF-treated group(n= 24) and sham-operated group(n= 20). The control group and G-CSF -treated group underwent injection of homologous microthrombotic particle suspension into left ventricle when clamping the ascending aorta. The sham-operated group were treated with saline.rhG-CSF(100 yg · kg<'-1> · d<'-1>) were injected subcutaneously for 5 days since 2 h after operation in C-CSF group, meanwhile, the control group and sham-operated group were treated with saline respectively. The rats were sacrificed at day 3,7,14 and 28 after operation. The mRNA expressions of Bcl-2, Bax, Fas, FasL and glyceraldehyde phosphate dehydrogenase (GAPDH) were evaluated by real time PCR. The ratio of Bcl-2/Bax was calculated. The protein expressions of easpase-3 and cleaved poly ADP-ribose polymerase (PARP) were detected by Western blot. Myocardial apoptosis and leftventricular function were checked byterminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL)staining and hemodynamics respectively. ResultsCompared with sham-operated group,the mRNA expression of Bcl-2, Bax, Fas and FasL were increased whereas the ratio of Bcl-2/Bax markedly decreased in control group(0.28±0.04 vs. 2.98±0.49), P<0.05.Simultaneously, the protein expressions of caspase-3 and cleaved PARP enhanced (0.762±0.129 vs. 0.133±0.027;0.992±0.146 vs. 0.386+0.074) ,all P<0.05. The myocardial apoptosis index was elevated(17.2±1.9 vs. 1.2±0.6)and the left ventricular function decreased significantly (P<0.05). Compared with control group, the mRNA expression of Bct-2 increased and that of Bax, Fas and FasL decreased in G-CSF-treated group. Meanwhile, the ratio of Bcl-2/Bax markedly increased(2.07±0.29 vs. 0.28±0.04)and the protein expression of caspase-3 and cleaved PARP decreased(0.371±0.041 vs. 0.762±0.129;0.548±0.093 vs. 0.992±0.146, all P<0.05). The myocardial apoptosis index was reduced (6.1±1.0 vs. 17.2±1.9)and the left ventricular function increased significantly (P<0.05).ConclusionsG-CSF could lighten the myocardial apoptosis and improve the left ventrieular functionafter CME.