肝十二指肠韧带内注射利多卡因对缺血再灌注损伤肝脏的影响

The protective effect on hepatic ischemia/reperfusion injury by lidocaine injection into hepatoduodenal ligament in rats

目的 :探讨肝十二指肠韧带内注射利多卡因减轻肝脏缺血 再灌注 (Ischemia reprefusion ,I R)损伤的有效性以及从蛋白质组水平研究其可能涉及的机制。方法 :4 6只SD大鼠随机分成I R组、利多卡因组和开腹组。检测各组血清丙氨酸转氨酶 (ALT)和门冬氨酸转氨酶 (AST) ,肝脏组织标本胎盘蓝染色分析。肝脏组织的蛋白质组学分析采用双向聚丙烯酰胺凝胶电泳 (2 DPAGE)、质谱 (MALDI TOF MS)方法。结果 :利多卡因组ALT和AST较I R组显著降低 (ALT :t=2 .5 99,P <0 .0 2 ;AST :t=2 .992 ,P <0 .0 1) ,胎盘蓝染色的无活性肝细胞较I R组也明显减少。利多卡因组的 2 DPAGE图谱较I R组发生了改变 ,质谱鉴定出 11个差异表达的蛋白质 ,其中 6个上调表达 ,5个下调表达。结论 :肝十二指肠韧带内注射利多卡因预处理有效地减轻了大鼠肝脏随后的I R损伤 ,是一种保护面临I R损伤肝脏的新方法。蛋白质组学研究可见 ,利多卡因预处理改变了肝脏I R后的蛋白质表达。

Objective: To investigate the potential protective effect of lidocaine injected into hepatoduodenal ligament on hepatic I/R injury and its mechanism on the level of proteomics. Methods: 46 SD rats were randomly divided into 3 groups. I-R group: Animals were subjected to hepatic 40-minute I-R. Lidocaine group: Previous to hepatic 40 min I-R, 0.4% lidocaine hydrochloride was injected into hepatoduodenal ligament for 10 minutes. Laparotomy group: Laparotomy was performed without any treatments for 90 minutes. Blood samples of each group were processed to determine plasma alanine transaminase (ALT) and aspartate transaminase (AST). Hepatic tissues were examined pathologically by trypan blue uptake of hepatocytes. Proteomic analysis of liver tissues were performed by two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: A significant decrease of ALT and AST was noted for lidocaine group VS I-R group(ALT: t=2.599, P<0.02; AST: t=2.992, P<0.01). The protective effect of hepatocytes in lidocaine group was confirmed histologically by a marked reduction of nonviable hepatocytes with trypan blue uptake. Eleven proteins altered their expressions after the lidocaine pretreatment, of which six were up-expressed, five down-expressed. Conclusion:Previous to hepatic I-R, the pretreatment with lidocaine injected into hepatoduodenal ligament as a novel approach attenuates hepatic warm I-R injury of rats effectively, and alters some protein expressions of rat liver of I-R injury.