异丙酚对兔肝缺血/再灌注损伤中一氧化氮和内皮素的干预

Effect of propofol on nitric oxide and endothelin in the reperfusion injury after hepatical ischemia in rabbits

目的 探讨一氧化氮 (NO)和内皮素 (ET)在肝缺血 /再灌注损伤 (HIRI)中的作用及异丙酚对其的影响。方法 实验兔分为假手术对照组 (n =10 )、肝缺血 /再灌注组 (n =10 )及肝缺血 /再灌注 +异丙酚治疗组 (n =10 ) ;分别检测缺血前、缺血 4 5min和再灌注 4 5min 3个时点的指标变化。用硝酸还原酶法检测血浆及肝组织一氧化氮代谢产物 (NOP)含量 ,放射免疫法测定ET水平 ,赖氏法测定谷丙转氨酶 (ALT)活性 ,并行肝组织电镜观察。结果 肝缺血 /再灌注期间 ,血浆NOP明显低于假手术对照组 ,而ET及ALT显著高于假手术对照组 ,尤以再灌注 4 5min变化显著 (P <0 0 5和P <0 0 1) ;肝组织NOP明显低于假手术对照组 ,而ET显著高于假手术对照组 (P <0 0 5和P <0 0 1) ;肝细胞形态学发生异常改变。异丙酚可逆转上述指标的异常变化。结论 缺血 /再灌注导致血管内皮功能紊乱 (即NO水平下降和ET水平升高 ) ,在HIRI发生发展中起介导作用 ;异丙酚通过保护肝窦内皮 ,提高机体内NO水平和降低机体内ET水平 ,从而减轻HIRI。

Objective To study the role of nitric oxide and endothelin during hepatic ischemia-reperfusion injury (HIRI) and effect of propofol(PPF). Methods The rabbits were randomly divided into three groups (n=10, in each), sham operated group (S), HIRI group (I/R) and HIRI+PPF group (PPF). Plasma nitric oxide products (NOP, in terms of NO 2-/NO 3-) contents, endothelin (ET) levels, and alanine aminotransferase (ALT) activities were measured before ischemia, 45 minutes after ischemia and 45 minutes after reperfusion. Meanwhile NOP and ET concentration in liver tissue were measured, and the change of hepatocytes morphologically was observed under electron microscope at 45 minutes after reperfusion. Results Compared with group A, NOP decreased and ET as well as ALT increased at 45 minutes (P<0.05 and P<0.01) and more significantly at 45 minutes after reperfusion (P<0.05 and P<0.01) in plasma, and NOP decreased as well as ET increased (P<0.05 and P<0.01) at 45 minutes after reperfusion in liver tissue and there were abnormal changes of hepatocytes morphologically at 45 minutes after reperfusion; propofol reversed the results of mentioned indices as above markedly. Conclusion The ischemia-reperfusion results in dysfunction of the endothelium (NO level decreasing and ET level increasing) which is an important factor during HIRI, propofol reduces HIRI by protecting hepatic sinus endothelium (raising NO level and dropping ET level).