Effects On Neural Apoptosis Following Preconditioning With Nicardipine Associated Propofol In Gerbils

BackgroundCerebral ischemia reperfusion damage is a kind of delayed neuronal death ( DND). A lot of investigations have showed that DND is closely related to apoptosis. Cell apoptosis is also called programmed cell death(PCD)that is a kind of positive death other than normal cell death and gene regulation. It has been investigated that cell apoptosis is the mechanism of cerebral ischemia toleration possibly.Recently, there are many reports on cerebral protection. Among them, the study of preconditioning is popular. Cerebral ischemia preconditioning is still a long way from clinical application, so the study of cerebral preconditioning has developed from ischemia to drugs. Nicadipine is a new "L" type of calciumions antagonist which can protect cerebral cell from ischemia reperfusion damageand propofol is an intravenous anesthetic which have a wide clinical application.ObjectiveTo investigate the effects of preconditioning with nicardipine and propofol on gerbils neuron apoptosis and study the relation between the expression of Bcl-2 protein and protection against ischemic neuronal damage by preconditioning with them. On the other hand, the research showed neural apoptosis induced by cerebral ischemia reached its peak after 72 h. Therefore in this study, we investigatet the percentages of apoptotic cells induced by ischemia reperfusion afer 72 h with TUNEL technology to study whether preconditioning with nicardipine and propofol has effect on gerbils neuron apoptosis and to investigate the relation between the expression of Bcl-2 protein and protection against ischemic neuronal damage by preconditioning with them to bring the mechanism of protection to light.MethodsThe cerebral ischemia was induced by occlusion of bilateral common carotid arteries. Fifty gerbils were divided randomly into five groups of ten animals each after injecting sodium pentobarbital into their abdominal cavities : sham operative control group(group A, n=10); ischemic control group(group B, n=10 )with a 5-min cerebralischemia and following 72h reperfusion ; nicardipine preconditioning group(group C, n=10): Nic(0.2mg/kg) was iv 30 min prior to ischemia;propofol preconditioning group (group D, n=10):propofol(100mg/kg) was injected into abdominal cavity 30 min prior to ischemia; nicardipine associated propofol preconditioning group(group E, n=10): Nic(0.2mg/kg, iv) associated propofol (100mg/kg, injected into abdominal cavity) 30 min prior to ischemia. The animals were sacrificed immediately at the end of the experiment. Neural apoptosis was identified by terminal deoxynucleotidyl transferse-mediated dUPT-biotin nick end labeling (TUNEL) and Paraffin sections of cortex were used for Bcl-2 protein immunohistochemical staining.Results(1) The apoptotic cells can hardly be seen in group A andThe apoptotic cells percentages in group E were markedly lower than in group B, C and D ( P<0. 05;(2) Bcl-2 protein immunoreactivity( the intensity ofstaining) in group E significantly increased compared with that in the other groups (P<0.05, P<0. 05; P<0. 05).Conclusions(1) Neural apoptosis after transient cerebral ischemia reperfusion.(2) To preconditioning with nicardipine associated propofol can decrease the apoptotic cells percentages potently against ischemia reperfusion brain damage .(3) The high expression of Bcl-2 protein can inhibit neural apoptosis effectively.(4) The effective of preconditioning with nicardipine associated propofol on neural apoptosis in gerbils is closely related to the expression of Bcl-2 protein.