摘要：
目的：比较不同剂量羟丁酸钠对离体大鼠缺血再灌注损伤心肌脂质过氧化作用的影响。方法将24只成年Wistar大鼠随机分为4组(n=6)：心肌缺血再灌注组(I/R组),1 mmol/L羟丁酸钠组(RL组),2．5 mmol/L羟丁酸钠组( RM组),10 mmol/L羟丁酸钠组( RH组)。采用 Langendorff离体心脏缺血再灌注模型,四组均以K-H液平衡灌注10 min,再以K-H液及1、2．5、10 mmol/L羟丁酸钠的K-H液分别灌注10 min,然后全心停止灌注25 min,再分别继续灌注30 min。测定冠脉流出液总乳酸脱氢酶( LDH)活性；灌注末,用2．5%戊二醛固定左室心肌组织,观察心肌超微结构；留取心尖部心肌组织以检测8-异前列腺素、超氧化物歧化酶(SOD)活性。结果与IR组比较,RL组8-异前列腺素含量、SOD及LDH活性差异均无统计学意义(P>0．05),超微结构也未见损伤减轻；RM组8-异前列腺素含量、SOD活性差异均无统计学意义(P>0．05),LDH活性差异有统计学意义(P0．05),超微结构可见损伤加重。结论羟丁酸钠(1、2．5 mmol/L)不能降低心肌缺血再灌注损伤大鼠的8-异前列腺素含量,抑制脂质过氧化反应；但是2．5 mmol/L羟丁酸钠能减轻大鼠心肌缺血再灌注损伤；10 mmol/L羟丁酸钠则加重了脂质过氧化反应和心肌缺血再灌注损伤。%Objective To compare the effects of three different doses of gamma-hydroxybutyrate on lipid per-oxidation in isolated rat hearts after myocardial ischemia-reperfusion. Methods Twenty-four adult Wistar rats were randomly divided into 4 groups ( 6 rats in each group ):ischemia-reperfusion group ( I/R group ) , I/R + gamma-hydroxybutyrate (1,2. 5,10 mmol/L) groups (RL,RM,RH groups). The isolated rat hearts were perfused with Lan-gendorff perfusion system. All the rat hearts were initially perfused with Krebs-Henseleit ( K-H) solution for 10 min, then respectively perfused with K-H solution dissolved no gamma-hydroxybutyrate,gamma-hydroxybutyrate (1,2. 5, 10 mmol/L) for 10 min followed by 25 min global ischemia and 30 min reperfusion. The total lactate dehydrogenase ( LDH) of the reperfusion solution,levels of 8-isoprostane and SOD activity of apex of hearts were determined. The left ventricular tissues were used for observing myocardial ultrastructure. Results The levels of 8-isoprostane, LDH and SOD activity in group RL did not significantly differ from I/R group ( P>0. 05 ) . The myocardial ultrastructure also showed that group RL cannot lessened the myocardial I/R injury. Although levels of 8-isoprostane and SOD activity in group RM did not significantly differ from those in I/R group (P>0. 05),the LDH activity differed significantly(P<0. 05). The microscopic examination indicated that group RM can alleviate the myocardial I/R injury,but compared with I/R group,levels of 8-isoprostane and LDH were raised significantly ( P <0. 05 ) , the myocardial ultrastructure was injuried more seriously. Conclusion Gamma-hydroxybutyrate (1,2. 5 mmol/L) cannot decrease the levels of 8-isoprostane or inhibit lipid peroxidation. But 2. 5 mmol/L Gamma-hydroxybutyrate can alleviate the myocardial I/R in-jury. While 10 mmol/L Gamma-hydroxybutyrate can exacerbated lipid peroxidation and myocardial ischemia-reperfu-sion injury.
