丙戊酸治疗大鼠蛛网膜下腔出血后脑血管痉挛的机制研究

发布时间：2018-05-30 22:18

本文选题：蛛网膜下腔出血 + 脑血管痉挛　；参考：《浙江大学》2014年硕士论文

【摘要】：背景：蛛网膜下腔出血约占全部脑卒中的5%-10%,尽管随着诊断方法、血管介入手术技巧以及围手术期的处理已经取得的巨大进步,动脉瘤再出血造成的死亡明显下降,但蛛网膜下腔出血病人的预后并没有明显改善脑血管痉挛是造成蛛网膜下腔出血后引起迟发性缺血性神经功能障碍的主要原因。目前的他汀类药物,血管内皮素受体拮抗剂,硫酸镁等均不能改善预后,因此寻求新的预防血管痉挛的药物迫在眉睫。丙戊酸作为一种临床上常用的抗癫痫药物,近年来的研究表明它有神经保护作用。并且它主要是通过抗氧化,抗炎等作用。这给我们带来了启示,丙戊酸是否能预防血管痉挛。目的：本研究观察丙戊酸改善蛛网膜下腔出血后脑血管痉挛,并探讨丙戊酸减轻蛛网膜下腔出血后脑血管痉挛的机制。方法：采用血管内线栓穿刺法制作蛛网膜下腔出血模型,成年雄性大鼠被随机分为假手术组,蛛网膜下腔出血组、蛛网膜下腔出血+丙戊酸组。48小时后,测量基底动脉的血管壁厚度,血管内径；采用Western blot检测基底动脉组织P-ERK1/2蛋白表达水平；采用RT-PCR检测基底动脉中炎症因子IL-1β, IL-6, TNF-a的RNA含量。结果：经丙戊酸处理后,基底动脉的血管壁厚度明显变小,血管内径增大,丙戊酸处理后,基底动脉组织P-ERK1/2蛋白明显下降,炎症因子IL-β, IL-6, TNF-a的RNA含量也明显下调。结论：丙戊酸有效改善蛛网膜下腔出血后的脑血管痉挛,其可能的机制是下调P-ERK1/2蛋白,减轻炎症反应。
[Abstract]:Background: Subarachnoid hemorrhage accounts for about 5- 10 percent of all stroke, although with great progress in diagnostic methods, vascular interventional techniques, and perioperative management, the number of deaths from rebleeding from aneurysms has decreased significantly. However, the prognosis of patients with subarachnoid hemorrhage did not significantly improve the cerebral vasospasm is the main cause of delayed ischemic neurological dysfunction after subarachnoid hemorrhage. The current statins, endothelin receptor antagonists and magnesium sulfate can not improve the prognosis, so it is urgent to seek new drugs to prevent vasospasm. Valproic acid (valproic acid) is a commonly used antiepileptic drug. Recent studies have shown that valproic acid has neuroprotective effect. And it is mainly through anti-oxidation, anti-inflammatory and other effects. This tells us whether valproic acid can prevent vasospasm. Objective: The purpose of this study was to observe the effect of valproic acid on cerebral vasospasm after subarachnoid hemorrhage and to explore the mechanism of valproic acid in relieving cerebral vasospasm after subarachnoid hemorrhage. Methods: The model of subarachnoid hemorrhage was made by puncture of intravascular embolus. Adult male rats were randomly divided into sham operation group and valproic acid group after 48 hours of subarachnoid hemorrhage. The wall thickness of basilar artery was measured. The expression of P-ERK1/2 protein in basilar artery was detected by Western blot and the RNA content of IL-1 尾, IL-6 and TNF-a in basilar artery was detected by RT-PCR. Results: After valproic acid treatment, the thickness of basilar artery became smaller and the diameter of artery increased. After valproic acid treatment, the P-ERK1/2 protein of basilar artery decreased significantly, and the RNA content of IL- 尾, IL-6 and TNF-a decreased significantly. Conclusion: Valproic acid can effectively improve cerebral vasospasm after subarachnoid hemorrhage by down-regulating P-ERK1/2 protein and alleviating inflammation.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.35

【共引文献】