摘要
目的:观察1,6二磷酸果糖和镁离子的合成药果糖二磷酸镁对心肌缺血再灌注损伤过程中血清中肌酸激酶,乳酸脱氢酶,Mg2+浓度,心肌组织内超氧化物歧化酶,丙二醛浓度的影响,并与单用1,6二磷酸果糖或硫酸镁相比较。方法:实验于2004-10/2005-05在锦州医学院药理学实验室进行,取50只雄性SD大鼠随机分为5组,每组10只:①模型组:采用左冠状动脉下穿线,拉紧丝线引起心肌缺血,放松丝线给予再灌注的方法建立心肌缺血再灌注损伤动物模型,结扎冠脉左室前降支30min时经大鼠尾静脉注入生理盐水1mL,10min给药完毕,再灌注40min。②果糖二磷酸镁组:造模及给药时间和方法同模型组,注入药物为1mL果糖二磷酸镁(100mg/kg)。③1,6二磷酸果糖组:同前造模给药,药物为1mL1,6二磷酸果糖(106mg/kg)。④硫酸镁组:同前造模给药,药物为硫酸镁(30mg/kg)。⑤假手术组:完成模型全部操作,只穿线不结扎。各组大鼠在再灌注40min后,均经颈动脉取血采用比色法测定肌酸激酶,乳酸脱氢酶活力及Mg2+浓度;于实验结束后立即取左室游离心肌组织0.5g,采用羟胺法测定超氧化物歧化酶活力,采用硫代巴比妥钠比色法测定丙二醛含量。结果:50只大鼠进入结果分析。①血清中肌酸激酶活力:果糖二磷酸镁组、1,6二磷酸果糖组和硫酸镁组均低于模型组[(84.40±19.15),(86.90±5.68),(90.86±9.13),(105.43±3.95)μkat/L,P<0.05]。②血清乳酸脱氢酶活力:果糖二磷酸镁组、1,6二磷酸果糖组和硫酸镁组均低于模型组[(47.57±19.58),(50.94±3.86),(50.45±5.37),(68.59±11.74)μkat/L,P<0.01]。③血清中Mg2+浓度:果糖二磷酸镁组和硫酸镁组均高于模型组[(0.92±0.06),(0.91±0.04),(0.75±0.03)mmol/L,P<0.01]。④心肌组织超氧化物歧化酶活力:果糖二磷酸镁组和1,6二磷酸果糖组均高于模型组[(1.52±0.41),(1.44±0.39),(1.15±0.28)μkat/g,P<0.05]。⑤心肌组织内丙二醛含量:果糖二磷酸镁组和1,6二磷酸果糖组显著低于模型组[(17.08±23.12),(21.60±5.58),(50.13±18.21)nmol/g,P<0.01]。结论:果糖二磷酸镁对缺血再灌注心肌损伤具有保护作用,很可能是通过1,6二磷酸果糖和硫酸镁协同作用而产生,其效果优于单用1,6二磷酸果糖或硫酸镁。其保护作用机制与增加血清中Mg2+浓度和组织内超氧化物歧化酶含量,减少血清中肌酸激酶,乳酸脱氢酶活力和组织内丙二醛含量及抗脂质过氧化有关。
AIM: To observe the effect of magnesium fructose-1, 6-diphosphate that is the synthetic drug with fructose-1, 6-diphosphate and Mg^2+ during myocardial ischemia/reperfusion injury on the concentration change of creatine kinase (CK), lactate dehydrogenase (LDH) and Mg^2+ in the serum and superoxide dismutase (SOD) and malondialdehyde (MDA) in the myocardium, and compare the effect of fructose-1, 6-diphosphate and MgSO4.
METHODS: The experiment was performed in the Pharmacology Lab of Jinzhou Medical College from October 2004 to May 2005. Fifty SD male rats were selected and randomly divided into five groups with 10 rats in each group: ①model group: The models of myocardial ischemia/ reperfusion injury in anesthetized rats were established. The model was made with drawing then releasing the suture advanced around the left coronary artery in rats. 1 ml saline was injected into caudal vein of rats when the nlygcardial ischemia had passed 30 minutes in ten minutes, and then reperfusing for 40 minutes. ②FDP-M (magnesium fructose-1, 6- diphosphate) group: The model, the time and method of injection were all same to the control group. The drug was 1 ml FDP-M( 100 mg/kg).③FDP (fructose-1,6-dipbosphate) group: Establishing the same to the control group. The drug was 1 mL FDP (106 mg/kg). ④MgSO4 (magnesium sulfate) group: Establishing the same to the control group. The drug was MgSO4 (30 mg/kg). ⑤Sham operation group: The model was performed all the steps only not to draw the suture. After reperfusion for 40 minutes of rats in every group, activities of CK and LDH and concentration of Mg^2+ in the blood serum gained from carotid artery were detected with ehromatometry. 0.5 g myocardium of the left ventricle was gotten in the same time at the end of the experiment. Activity of SOD and content of and MDA were detected with hydroxylamine method and thiobarbituric acid calorimetric method.
RESULTS: All the 50 rats were involved in the analysis of results. ① Activity of serum CK: It was lower in the FDP-M group, FDP group and MgSO4 group than that in the model group [(84.40±19.15),(86.90±5.68), (90.86±9.13), (105.43±3.95)μkat/L,P 〈 0.05]. ②Activity of serum LDH: It was lower in the FDP-M group, FDP group and MgSO4 group than that in the model group [(47.57±19.58),(50.94±3.86),(50.45±5.37),(68.59±11.74)μkat/L,P 〈 0.01]. ③Concentration of serum Mg^2+: It was higher in the FDP-M group and MgSO4 group than that in the model group[(0.92±0.06), (0.91±0.04), (0.75±0.03)mmol/L,P 〈 0.01]. ④Activity of SOD in myocardium: It was higher in the FDP-M group and the FDP group than that in the model group [(1.52±0.41), (1.44±0.39), (1.15±0.28)μkat/g,P 〈 0.05]. ⑤Content of MDA in myocardium: It was lower significantly in the FDP-M group and the FDP group than that in the model group[(17.08±23.12),(21.60±5.58), (50.13±18.21) nmol/g, P〈 0.01].
CONCLUSION: Magnesium fructose-1, 6-diphosphate has protective effects on myocardial ischemia reperfusion injury, which is achieved possibly by partial synergetic action of FDP and MgSO4. The effect is better than using FDP or MgSO4 solely. The protective effects may be related with increasing concentration of Mg^2+ and SOD, relieving activities of serum CK and LDH, content of MDA as well as anti-lipid peroxidation.
出处
《中国临床康复》
CSCD
北大核心
2006年第4期73-75,共3页
Chinese Journal of Clinical Rehabilitation