硫酸镁抗自由基作用的量效分析

Dose-effect analysis of magnesium sulfate against free radicals

目的:探讨具有抗自由基作用的硫酸镁在大鼠脑缺血后最佳治疗剂量与其脑保护作用的关系。方法:实验于2004-10-05/12-19在锦州医学院科学实验中心完成。取SD大鼠60只,随机将大鼠分为正常组、缺血组及硫酸镁80,160,320mg/kg组5组,每组12只。除正常组不插入栓线外,其余4组采用线栓法制备大鼠大脑中动脉缺血模型,术后即刻正常组与缺血组腹腔注射生理盐水1mL,硫酸镁各剂量组按上述剂量腹腔注射250g/L硫酸镁注射液(均用盐水稀释至1mL),观察24h后脑组织病理变化,脑匀浆液中超氧化物歧化酶活性、丙二醛含量。结果:经补充后60只大鼠进入结果分析。①脑组织病理变化:硫酸镁各剂量组与缺血组比较,梗死区缩小,坏死程度减轻,而且随着剂量的加大梗死周边结构完整的神经细胞数则明显增多。②超氧化物岐化酶活性:缺血组、硫酸镁80mg/kg组均显著低于正常组[(23.08±2.78),(27.65±4.33),(34.56±4.70)NU/mg,P<0.01],硫酸镁160,320mg/kg组则显著高于缺血组[(30.23±5.03),(32.72±4.76)NU/mg,P<0.01],且硫酸镁80,320mg/kg两组间差异显著(P<0.05)。③丙二醛含量:缺血组、硫酸镁80mg/kg组均显著高于正常组[(3.52±0.69),(2.68±0.74),(1.44±0.55)μmol/g,P<0.01],硫酸镁160,320mg/kg组则显著低于缺血组[(2.05±0.57),(1.58±0.69)μmol/g,P<0.01],且硫酸镁80,320mg/kg两组间差异显著(P<0.05)。结论:①脑缺血早期应用硫酸镁可有效减轻脑组织的损害程度,减轻脑组织的炎症反应,而且大剂量组的保护作用更加明显。②硫酸镁减少自由基的生成,提高抗自由基的能力,且与硫酸镁剂量有明显的依赖关系,大剂量疗效更佳。

AIM:To investigate the relationship between the optimal doses and the protective effects of magnesium sulfate against the brain injury due to free radical in rats with cerebral ischemia.METHODS:The experiment was carried out in Scientific Research Center of Jinzhou Medical College from October 5 to November 20,2004.Sixty SD rats were randomly and equally divided into control group,cerebral ischemia group and magnesium sulfate 80,160,320 mg/kg treatment groups. Embolization thread was inserted into all the rats except those in the control group for the establishment of rat models of middle cerebral artery ischemia by middle cerebral artery occlusion.Immediately after operation,the rats in the control and cerebral ischemia groups were injected with 1 mL normal saline,and those in the magnesium sulfate treatment groups were intraabdominally injected their corresponding doses of magnesium sulfate at 250 g/L after diluted into 1 mL with normal saline. The histopathological changes of cerebral tissues were observed after 24 hours,meanwhile the activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) were measured in brain homogente.RESULTS:By supplement,60 rats were involved in the result analysis.①For the histopathological changes:Compared with the cerebral ischemia group,the infraction area was smaller and the degree necrosis lower in the magnesium sulfate treatment groups;Moreover,the higher the dose of magnesium sulfate was,the more was the amount of neurons with complete structure around infraction area.②The activity of SOD was significantly lower in the cerebral ischemia group[(23.08±2.78) NU/mg] and the 80 mg/kg magnesium sulfate treatment group[(27.65±4.33) NU/mg] than in the control group[(34.56±4.70) NU/mg](P< 0.01),significantly higher in the 160 and 320 mg/kg magnesium sulfate treatment groups[(30.23±5.03),(32.72±4.76) NU/mg respectively] than in the cerebral ischemia group(P< 0.01),and significantly different between the 80 mg/kg and 320 mg/kg magnesium sulfate treatment groups(P< 0.05).③The content of MDA was significantly higher in the cerebral ischemia and 80 mg/kg magnesium sulfate treatment groups[(3.52±0.69) μmol/g and (2.68±0.74) μmol/g,respectively] than in the control group[(1.44±0.55) μmol/g](P< 0.01),but significantly lower in the 160 and 320 mg/kg magnesium sulfate treatment groups[(2.05±0.57) and (1.58±0.69) μmol/g respectively] than in the cerebral ischemia group(P< 0.01),and significantly different between the 80 mg/kg and 320 mg/kg magnesium sulfate treatment groups(P< 0.05).CONCLUSION:①The application of magnesium sulfate in early cerebral ischemia can effectively alleviate the damage to cerebral tissues and relieve the inflammatory reaction,and especially,highdose magnesium sulfate has a protective function.②Magnesium sulfate decreases the production of free radical and enhances the function of antifree radical in a dosedependent manner.