大鼠心脏缺氧缺血再灌注损伤与果糖二磷酸镁的保护途径

Myocardial hypoxia ischemia-reperfusion injury in rats and the protective pathway of magnesium fructose diphosphate

目的:观察具有改善心脏能量代谢作用的果糖二磷酸镁对实验性大鼠心肌缺血再灌注损伤的保护性途径。方法:实验于2005-03在锦州医学院药理学实验室完成。24只SD大鼠随机分为3组:对照组、缺血再灌注组和果糖二磷酸镁组,每组8只。3组大鼠均实施主动脉递引灌流,采用Langendorff方法用KH缓冲液[(NaCl118.5,NaCO325.0,KH2PO41.2,KCl4.8,MgSO41.2,CaCl22.0,葡萄糖1.0)mmol/L]制备离体大鼠心脏缺血再灌注模型,将果糖二磷酸镁(2.4mmol/L)加入灌流液内,停灌时间30min,再灌注时间1h。分别在心脏灌流稳定20min,再灌注60min记录左室收缩压、左室压力变化速率,并收集1min冠状动脉血流量。取左心室标本测总超氧化物歧化酶活性用黄嘌呤氧化酶法,测组织丙二醛含量用硫代巴比妥酸法。结果:24只SD大鼠均进入结果分析。①再灌注后左室收缩压比较:果糖磷酸镁组明显低于缺血再灌注组[(73.0±6.8,109.0±9.2)mmHg,(t=10.789,P<0.05)]。②再灌注后左室压力变化速率比较:缺血再灌注组明显低于对照组[(913±233,1889±304)mmHg/s,(t=6.756,P<0.01)]。③再灌注后心脏冠状动脉血流量比较:果糖磷酸镁组明显高于缺血再灌注组[(4.6±0.4,3.5±0.5)mL/min,(t=2.693,P<0.05)]。④再灌注后左心室肌组织总超氧化物歧化酶活性比较:果糖磷酸镁组明显高于缺血再灌注组[(33.06±3.03,22.18±4.79)NU/mg,(t=8.123,P<0.01)]。⑤再灌注后左心室肌组织丙二醛含量比较:缺血再灌注组组明显高于对照组[(10.00±1.13,2.56±0.63)nmol/mg,(t=18.76,P<0.01)]。结论:果糖二磷酸镁对再灌注损伤心肌可改善其收缩功能,并降低心肌组织中的丙二醛含量,从而减少氧自由基的产生,起到抗脂质过氧化而保护心肌的作用。

AIM: To observe pathway of magnesium fructose diphosphate, which has the effect in ameliorating cardiac energy metabolism, against myocardial is-chemia-reperfusion injury in experimental rats. METHODS: The experiment was carried out in the pharmacological labo-ratory of Jinzhou Medical College in March 2003. Twenty-four SD rats were randomized into three groups with 8 rats in each group: con-trol group, is-chemia-reperfusion group and magnesium fructose diphos-phate group. All the rats in the 3 groups were treated with aortic gradual perfu-sion, and iso-lated models of myocardial ischemia-reperfu-sion were pre-pared by us-ing the Langendorff method with KH buffer (NaCl: 118.5, NaCO3: 25.0, KH2PO4: 1.2, KCl:4.8, MgSO4: 1.2, CaCl2: 2.0, glucose: 1.0 mmol / L), magnesium fructose diphosphate (2.4 mmol / L) was added to the perfused liquid, per-fusion was stopped for 30 min-utes, time of reper-fusion was 60 minutes. Left ventricular systolic pres-sure, rate of change of left ventricu-lar pres-sure were recorded and 1-minute coronary arterial blood flow was collected at 20 minutes of sta-ble perfusion and 60 minutes of reperfusion respec-tively. Left ventricu-lar samples were taken to detect the activity of super-oxide dismutase with the method of xanthine oxidase and determine the content of malondialdehyde with the method of thiobar-bituric acidreacting sub-stances. RESULTS: All the 24 SD rats were involved in the analysis of re-sults. ① Left ventricular systolic pressure after reperfusion was obvi-ously lower in the magnesium fructose diphosphate group than in the ischemia-reperfusion group [(73.0 ± 6.8), (109.0 ± 9.2) mm Hg, t= 10.789, P < 0.05]. ② The rate of change of left ventricular pressure after reper-fusion was markedly lower in the ischemia-reperfusion group than in the control group [(913 ± 233), (1 889 ± 304) mm Hg / s, t= 6.756, P< 0.01]. ③ Coronary arterial blood flow in heart after reperfusion was obviously higher in the magnesium fructose diphosphate group than in the ischemia-reperfusion group [(4.6 ± 0.4), (3.5 ± 0.5) mL per minute, t= 2.693, P < 0.05]. ④ The activity of superoxide dismutase in left ventricular tissue after reperfusion was obviously higher in the magnsi-um fructose diphosphate group than in the ischemia-reperfusion group [(33.06 ± 3.03), (22.18 ± 4.79) NU / mg, t= 8.123, P < 0.01]. ⑤ The con-tent of malondialdehyde in left ventricular tissue after reperfusion was obviously higher in the ischemia-reperfusion group than that in the control group [(10.00 ± 1.13), (2.56 ± 0.63) nmol / mg, t=18.76, P < 0.01]. CONCLUSION: Magnesium fructose diphosphate can ameliorate the systolic function of the myocardium after reperfusion injury, and de-crease the content of malondialdehyde in the myocardial tissue, so that it reduces the produce of oxygen-derived free radicals, and then plays a role in relieving lipid peroxidation and protecting myocardium.