【摘要】：背景與目的臨床試驗(yàn)證明,系統(tǒng)性給予硫酸鎂對腦卒中患者無明顯療效。依據(jù)前人對硫酸鎂血腦屏障通透性以及腦缺血后血腦屏障損傷的病理生理學(xué)過程的研究結(jié)果,我們猜測,腦缺血后急性期血腦屏障構(gòu)造損傷之前鎂離子的血腦屏障通透性不高是臨床試驗(yàn)失敗的因素之一。我們首先確定血腦屏障對鎂離子非選擇性開放的時間,然后進(jìn)一步探討血腦屏障開放前給予血腦屏障高通透性的L-蘇糖酸鎂對短暫局灶性腦缺血大鼠的神經(jīng)保護(hù)作用。方法1、確定血腦屏障開放時間點(diǎn)。線栓阻塞左側(cè)大腦中動脈90min制作SD大鼠短暫局灶性腦缺血模型。于缺血后3h、6h、12h、24h腹腔注射硫酸鎂(2mM/kg),采集CSF,檢測鎂離子濃度,確定血腦屏障對鎂離子非選擇性開放的時間。2、探討血腦屏障開放前給予L-蘇糖酸鎂對局灶性腦缺血大鼠的神經(jīng)保護(hù)作用。實(shí)驗(yàn)大鼠隨機(jī)分為4組:假手術(shù)組、模型組、硫酸鎂組、L-蘇糖酸鎂組。于缺血后24h取腦,新鮮腦組織行TTC染色標(biāo)記腦梗死灶,并計(jì)算梗死體積。結(jié)果1、血腦屏障對鎂離子非選擇性開放的時間。與正常組相比,缺血后3h、6h腹腔注射硫酸鎂組的CSF鎂濃度無顯著性差異,缺血12h、24h組的CSF鎂濃度明顯升高(P0.05)。2、L-蘇糖酸鎂對局灶性腦缺血大鼠的神經(jīng)保護(hù)作用。假手術(shù)組腦組織未見梗死灶形成;模型組大鼠腦梗死體積百分比為41.9±4.3%;硫酸鎂組腦梗死體積百分比為22.2±3.4%;L-蘇糖酸鎂組腦梗死體積百分比為13.8±3.8%。與正常組相比,模型組大鼠腦梗死體積明顯增大(P0.01);與模型組相比,硫酸鎂組、L-蘇糖酸鎂組大鼠腦梗死體積均顯著減小(P0.01);且L-蘇糖酸鎂組腦梗死體積比硫酸鎂組減少的更加明顯(P0.05)。結(jié)論1、腦缺血后血腦屏障對鎂離子非選擇性開放在6h-12h之間;2、血腦屏障開放前給予L-蘇糖酸鎂比硫酸鎂對局灶性腦缺血大鼠有更好的神經(jīng)保護(hù)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 鹵4.3, and that in magnesium sulfate group was 22.2 鹵3.4. The percentage of cerebral infarction volume in magnesium sulfate group was 13.8 鹵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.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R743.31

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