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

[目的 ]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(36 9.4 9± 4 8.6 8)U/L、AST(6 1 .2 3± 1 4 .95 )U /L、LDH(785 .5 3± 1 1 3.5 3)U /L、血浆内皮素 (4 7.4 9± 1 1 .5 8) μg/L、肝组织MDA(2 5 .2 0± 2 .93)nmol/mg水平均显著增高 (P <0 .0 5 ) ,细胞凋亡增加 (AI =1 7.6 8±1 .91 % ,P <0 .0 5 ) ,肝组织SOD明显减少 (1 9.0 3± 2 .37)U /mg ,P <0 .0 5。再灌注前使用GHB可以明显减轻上述改变 (P <0 .0 5 ) ,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。

To investigate whetherγ-Hydroxybutyrate (GHB) provides protection against hepatic warm ischemia-reperfusion injury. 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. 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.