异丙酚后处理联合缺血后处理对大鼠肝脏缺血再灌注损伤的影响

Effect of postcondifioning with propofol and ischemia on hepatic ischemia-reperfusion injury in rats

目的探讨异丙酚后处理联合缺血后处理对大鼠肝脏缺血再灌注损伤的影响。方法健康雄性sD大鼠30只，体重200～250g，随机分为5组（n=6），假手术组（I组）仅开腹；缺血再灌注组（Ⅱ组）肝脏缺血1h再灌注4h；缺血后处理组（11组）肝脏缺血1h后，再灌注10s，缺血10S，重复6次进行缺血后处理；异丙酚后处理组（Ⅳ组）肝脏缺血lh后经尾静脉注射异丙酚10mg／kg，随后静脉输注异丙酚40mg·kg^-1·h^-1 1h；异丙酚后处理＋缺血后处理组（V组）肝脏缺血1h后进行异丙酚后处理及缺血后处理。于再灌注4h时测定血清ALT活性、肝组织MDA含量、SOD活性、Bcl-2及Bax的蛋白表达水平，电镜下观察肝细胞超微结构。结果与I组比较，Ⅱ组～Ⅴ组血清ALT活性及肝组织MDA含量升高，肝组织Bcl-2蛋白表达上调，Ⅲ组-Ⅴ组肝组织SOD活性升高，Ⅱ组、Ⅲ组及Ⅴ组肝组织Bax蛋白表达上调（P〈0．05或0．01）；与Ⅱ组比较，Ⅲ组～Ⅴ组血清ALT活性及肝组织MDA含量降低，肝组织SOD活性升高，Bcl-2蛋白表达上调，Bax蛋白表达下调（P〈0．05或0．01）；与Ⅲ组比较，Ⅳ组血清ALT活性及肝组织MDA含量降低（P〈0．05或0．01）。Ⅲ组～Ⅴ组肝组织病理学损伤较Ⅱ组明显减轻。结论异丙酚后处理联合缺血后处理可减轻大鼠肝脏缺血再灌注损伤，与异丙酚后处理单独应用时效果相同，其机制可能与抑制肝组织脂质过氧化反应及细胞凋亡有关。

Objective To investigate the effect of posteonditionlng with propofol and ischemia on the hepatic ischemia-reperfusion （I/R） injury in rats. Methods Thirty male SD rats weighing 200-250 g were randomly divided into 5 groups of 6 animals each： group I sham operation （group S）; group II I/R; group m ischemic postconditioning （group IPC） ; group iV propofol postconditioning （group PPC） and groupV IPC ＋ PPC. In group II - V the hepatic arteries and veins of middle and left lobes were occluded for 1 h followed by 4 h reperfusion. Iscbemia of the liver was confirmed by the color of the liver turning from red to gray. In group III and V the livers were subjected to six episodes of 10 s ischemia at 10 s intervals at the end of 1 h ischemia before 4 h reperfusion. In group IV and V 0.5 % propofol 10 mg/kg was given iv at the end of ischemia followed by propofol infusion at 40 mg·kg^-1·h^-1. Blood samples were taken at the end of 4 h reperfusion for determination of serum ALT activity. Mean-while liver specimens were taken for electron microscopic examination and determination of MDA content and SOD activity. Results I/R significantly increased serum ALT activity and MDA content in the liver and decreased liver SOD activity in group II . The I/R-induced changes were significantly attenuated by propofol and/or ischemic postconditioning in group III, IV and V. I/R significantly increased Bcl-2 and Bax protein expression in the liver cells. Propofol and/or ischemic postconditioning increased Bcl-2 protein expression further but decreased Bax protein expression in group III, IV and V as compared with group II （group I/R）. Electron microscopic examination showed that the pathologic changes induced by I/Rwere less severe in group III, IV and V than in group I/R. Conclusion Postconditioning with propofol and ischemia can reduce the hepatic I/R injury and the mechanism may be related to inhibition of lipid peroxidation and apoptosis, but the efficacy is the same as that of propofol postconditioning alone.