丙泊酚静脉与颈内动脉输注对体外循环大鼠海马神经元凋亡的影响

目的比较丙泊酚静脉内输注与颈内动脉输注对中低温体外循环大鼠神经元凋亡和外周循环的影响。方法建立大鼠CPB模型,随机分成五组,假手术组(NonCPB组),体外循环组(CPB组),CPB+propofol2mg·kg-1·h-1静脉组(P2V组),CPB+propofol10mg·kg-1·h-1静脉组(P10V组)及CPB+propofol2mg·kg-1·h-1颈内动脉组(P2a组)。术中监测MAP、HR变化。TUNEL法检测神经元凋亡,电镜进行超微结构观察,RTPCR法检测bax和bcl2mRNA表达,Westernblot检测bax和bcl2蛋白表达。结果TUNEL检测结果显示P10V组和P2a组凋亡轻于CPB组(P<0.05);电镜显示P10V组和P2a组神经元损伤轻于CPB组(P<0.05);P2V组与CPB组差异无统计学意义。与假手术组相比,CPB组baxmRNA和bcl2mRNA表达明显增强(P<0.05);P10V组和P2a组baxmRNA表达弱于CPB组(P<0.05),bcl2mRNA表达强于CPB组(P<0.05);P2V组与CPB组差异无显著性。Westernblot检测显示相同的变化趋势。循环监测显示P10V组出现HR增快,MAP下降,而2mg.kg-1·h-1的丙泊酚无论何种途径给药,均无明显的循环抑制。结论小剂量丙泊酚颈内动脉连续输注能明显抑制体外循环大鼠海马神经元凋亡,具有明显的脑保护作用,且对循环抑制轻微。

Effect of intracarotid or intravenous injection of propofol on the neuronal apoptosis of hippocampus in rats undergoing cardiopulmonary bypass

Aim To compare the different effect of intracarotid and intravenous injection of propofol on the neuronal apoptosis of hippocampus in rats undergoing cardiopulmonary bypass.Methods Fifty rats were randomly assigned to five groups. Shame group (Group Non-CPB,n=10); group cardiopulmonary bypass(group CPB,n=10);group intravenous injection of propofol 2 mg·kg -1·h -1 (group P_ 2V,n=10);group intravenous injection of propofol 10mg.kg -1·h -1 (group P_ 10V,n=10);group intracarotid injection of propofol 2 mg·kg -1·h -1 (group P_ 2a,n=10).Mean arterial pressure(MAP)and heart rate(HR) were monitored. Changes of the neuronal apoptosis of hippocampus were observed with TUNEL staining, Bax and bcl-2 mRNA and protein expressions were measured by RT-PCR and Western blot. In addition,neuronal ultrastructures were observed. Results Neuronal apoptosis and changes of neuronal ultrastructures of hippocampus were attenuated in group P_ 2a and P_ 10V,but the apoptosis of neurons was not attenuated in group P_ 2v. Bcl-2 and Bax mRNA expression increased undergoing CPB. Bax mRNA expression decreased after CPB in group P_ 2a and P_ 10V. Bcl-2 mRNA expression increased in group P_ 2a and P_ 10V. But Bcl-2 and Bax mRNA expression in group P_ 2V was not significantly different compared with that of group CPB. Bcl-2 and Bax protein expression measured by Western blot showed the same trend with mRNA expressions. Compared with baseline values, MAP and HR in group P_ 2V and P_ 2a remained unchanged. But the MAP and HR in group P_ 10V changed compared with group CPB and baseline value.Conclusions intracarotid injection of propofol attenuated the injury of brain at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects.