血脑屏障开放前给予L-苏糖酸镁对短暂局灶性脑缺血大鼠保护作用的研究

发布时间：2018-08-24 07:37

【摘要】：背景与目的临床试验证明,系统性给予硫酸镁对脑卒中患者无明显疗效。依据前人对硫酸镁血脑屏障通透性以及脑缺血后血脑屏障损伤的病理生理学过程的研究结果,我们猜测,脑缺血后急性期血脑屏障构造损伤之前镁离子的血脑屏障通透性不高是临床试验失败的因素之一。我们首先确定血脑屏障对镁离子非选择性开放的时间,然后进一步探讨血脑屏障开放前给予血脑屏障高通透性的L-苏糖酸镁对短暂局灶性脑缺血大鼠的神经保护作用。方法1、确定血脑屏障开放时间点。线栓阻塞左侧大脑中动脉90min制作SD大鼠短暂局灶性脑缺血模型。于缺血后3h、6h、12h、24h腹腔注射硫酸镁(2mM/kg),采集CSF,检测镁离子浓度,确定血脑屏障对镁离子非选择性开放的时间。2、探讨血脑屏障开放前给予L-苏糖酸镁对局灶性脑缺血大鼠的神经保护作用。实验大鼠随机分为4组:假手术组、模型组、硫酸镁组、L-苏糖酸镁组。于缺血后24h取脑,新鲜脑组织行TTC染色标记脑梗死灶,并计算梗死体积。结果1、血脑屏障对镁离子非选择性开放的时间。与正常组相比,缺血后3h、6h腹腔注射硫酸镁组的CSF镁浓度无显著性差异,缺血12h、24h组的CSF镁浓度明显升高(P0.05)。2、L-苏糖酸镁对局灶性脑缺血大鼠的神经保护作用。假手术组脑组织未见梗死灶形成;模型组大鼠脑梗死体积百分比为41.9±4.3%;硫酸镁组脑梗死体积百分比为22.2±3.4%;L-苏糖酸镁组脑梗死体积百分比为13.8±3.8%。与正常组相比,模型组大鼠脑梗死体积明显增大(P0.01);与模型组相比,硫酸镁组、L-苏糖酸镁组大鼠脑梗死体积均显著减小(P0.01);且L-苏糖酸镁组脑梗死体积比硫酸镁组减少的更加明显(P0.05)。结论1、脑缺血后血脑屏障对镁离子非选择性开放在6h-12h之间;2、血脑屏障开放前给予L-苏糖酸镁比硫酸镁对局灶性脑缺血大鼠有更好的神经保护作用。
[Abstract]:Background & objective Clinical trials have shown that systemic magnesium sulfate has no significant effect on stroke patients. Based on previous studies on the permeability of the blood-brain barrier of magnesium sulfate and the pathophysiological process of blood-brain barrier injury after cerebral ischemia, we speculate, The low permeability of blood brain barrier before the structural damage of blood-brain barrier after cerebral ischemia is one of the factors that lead to the failure of clinical trials. We first determined the time of non-selective opening of blood-brain barrier to mg ~ (2 +), and then further investigated the neuroprotective effect of high permeability of blood-brain barrier (BBB) on transient focal cerebral ischemia in rats. Method 1. The opening time point of blood-brain barrier was determined. The model of transient focal cerebral ischemia in SD rats was established by occlusion of left middle cerebral artery (90min) with thread embolus. Magnesium sulfate (2mM/kg) was injected intraperitoneally at 3h, 6h, 12h and 24h after ischemia. The concentration of mg ~ (2 +) was measured by CSF, and the time of non-selective opening of blood-brain barrier to mg ~ (2 +) was determined to investigate the neuroprotective effect of magnesium L-sulfoxylate on focal cerebral ischemia rats before the opening of blood-brain barrier. Rats were randomly divided into 4 groups: sham operation group, model group and magnesium sulfate group. After 24 hours of ischemia, the fresh brain tissues were stained with TTC and the infarct volume was calculated. Results 1. The time of nonselective opening of BBB to mg ~ (2 +). Compared with the normal group, there was no significant difference in the concentration of CSF magnesium in the magnesium sulfate group 3 hours after ischemia, and the concentration of CSF magnesium in the 24 h group was significantly higher than that in the control group (P0.05). The percentage of cerebral infarction volume in model group was 41.9 卤4.3, and that in magnesium sulfate group was 22.2 卤3.4. The percentage of cerebral infarction volume in magnesium sulfate group was 13.8 卤3.8. Compared with the normal group, the cerebral infarction volume in the model group was significantly increased (P0.01); compared with the model group, the cerebral infarct volume in the magnesium sulfate group decreased significantly (P0.01), and the cerebral infarction volume in the magnesium L-threonoate group was significantly lower than that in the magnesium sulfate group (P0.05). Conclusion 1. Blood-brain barrier (BBB) has a better neuroprotective effect on focal cerebral ischemia rats than magnesium sulfate before opening of blood-brain barrier (BBB) by non-selective opening of mg ~ (2 +) between 6h-12h.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.31

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