目的 探讨磷丙泊酚钠后处理对大鼠肝脏缺血再灌注损伤的影响及是否呈剂量相关性。 方法 40只SD大鼠随机分为5组（每组n=8），即：假手术组（SP组）、生理盐水后处理组（NS组）、丙泊酚后处理组（PRO组）、低剂量磷丙泊酚钠[6 mg/（kg·h）]后处理组（LFOS组）、高剂量磷丙泊酚钠[12 mg/（kg·h）]后处理组（HFOS组）。除SP组外，其余4组在肝脏缺血60 min后给予药物后处理直至手术结束。在缺血60 min、再灌注60 min和120 min时采集血样，测定血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（ LDH）含量；在灌注120 min时取大鼠肝左外叶，用于HE染色，观察肝脏的形态学改变。 结果 与NS组相比，SP组、PRO组、LFOS组和HFOS组血清中的ALT、AST、LDH值明显降低（P＜0.05）；与SP组比较，PRO组、LFOS组、HFOS组和NS组的ALT、AST、LDH值升高（P＜0.05）；与PRO组比较，LFOS组的ALT、AST和LDH值差异无统计学意义（P＞0.05），HFOS组的ALT、AST和LDH值降低（P＜0.05）；LFOS组与HFOS组比较，HFOS组的ALT、AST和LDH值降低更为明显（P＜0.05）。 结论 磷丙泊酚钠后处理对大鼠肝脏缺血再灌注损伤具有保护作用，且高剂量磷丙泊酚钠[12 mg/（kg·h）]的保护作用更为明显，保护作用存在剂量依赖性。
ObjectiveTo investigate the effect of post-conditioning with fospropofol disodium on hepatic ischemiareperfusion (I/R) and its possible mechanism in rats. MethodsForty-eight Sprague-Dawley rats were randomly divided into four groups, including sham group (S), control group (C), propofol group (P) and fospropofol disodium group (F). According to the different periods after reperfusion, each group was further divided into 2-hour and 4-hour reperfusion subgroups respectively (n=6 in each subgroup), named S2h, C2h, P2h, and F2h subgroups and S4h, C4h, P4h, and F4h subgroups. The livers of rats were reperfused after hepatic ischemia for one hour. In the beginning of reperfusion, normal saline was infused intravenously in group S and group C continuously, propofol was infused intravenously in group P continuously, fospropofol disodium was infused continuously in group F. The blood was sampled at the end of ischemia and reperfusion for assay of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The bcl-2 and bax protein contents in liver tissue were detected by immunohistochemical analysis, and liver samples were stained with hematoxylin-eosine for histological observation and damage degree evaluation by counting the proportion of necrosis cells. ResultsThe activity of ALT and AST, the rate of necrosis cells and the amount of bcl-2 and bax protein after reperfusion in group C, group P and group F were higher than those in group S at matched reperfusion time points (P<0.05). The activity of ALT and AST, the proportion of necrosis cells and bax protein contents decreased in group P and group F, compared with group C at the same reperfusion time points, while the contents of bcl-2 protein were significantly increased (P<0.05). ConclusionFospropofol disodium can alleviate hepatic injury induced by ischemia-reperfusion in rats, in which the bcl-2 and bax protein may play important roles.