羟丁酸钠对肝热缺血再灌注损伤的保护作用

γ-Hydroxybutyrate protects liver against warm ischemia-reperfusion injury in rat

关键词:  羟丁酸钠  肝脏  再灌注损伤  凋亡

Key words:  γ-hydroxybutyrate  liver  reperfusion injury  apoptosis

摘要:

探讨羟丁酸钠（γ-hydroxybutyrate,GHB）对肝脏热缺血再灌注损伤的保护作用。［方法］　采用大鼠肝脏热缺血再灌注模型,观察肝脏组织形态学、酶学、脂质过氧化、细胞凋亡及血浆内皮素的变化。［结果］ 与假手术组相比,肝脏缺血再灌注损伤时,血清ALT（369.49±48.68） U/L、AST（61.23±14.95） U/L、LDH（785.53±113.53）U/L、血浆内皮素（47.49±11.58）μg/L、肝组织MDA（25.20±2.93） nmol/mg水平均显著增高（P<0.05）,细胞凋亡增加（AI=17.68±1.91%,P<0.05）,肝组织SOD明显减少（19.03±2.37） U/mg,P<0.05。再灌注前使用GHB可以明显减轻上述改变（P<0.05）,钠络酮可以部分阻断GHB的作用。［结论］ GHB可能通过抗脂质过氧化,下调肝脏内皮素的表达,改善微循环,减少肝细胞凋亡,从而减轻热缺血再灌注对肝脏的损伤作用。

Abstract:

To investigate whetherγ-Hydroxybutyrate (GHB) provides protection against hepatic warm ischemia-reperfusion injury.［Methods］　Using a rat model of hepatic warm ischemia-reperfusion,the hepatic histomorphology,enzymology,lipid peroxidation,apoptosis and the plasma level of Endothelin-1 were observed.　［Results］　After 30 minutes of partial hepatic ischemia,followed by 60 minutes of reperfusion,the serum level of ALT（369.49±48.68） U/L, AST（61.23±14.95） U/L and LDH（785.53±113.53） U/L and the plasma level of Endothelin-1（47.49±11.58）μg/L increased significantly (P<0.05) accompanied with an increase of apoptotic index (AI) from (0.28±0.25)% to (17.68±1.91)% when compared to the sham group.The hepatic concentrations of MDA（25.20±2.93） nmol/mg，P<0.05. showed an evidently increase while the activities of SOD（19.03±2.37) U/mg，P<0.05 showed a markedly decrease. GHB pretreatment prevented hepatic warm ischemia-reperfusion injury significantly (P<0.05), whereas naloxone partially blocked this protective effects. ［Conclusion］　GHB may provide significant protection against hepatic warm ischemia-reperfusion injury via several different mechanisms.