【作者】 王科；

【导师】 陈高；

【作者基本信息】 浙江大学 ， 外科学， 2014， 硕士

【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。更多还原

【Abstract】 Background:Subarachnoid hemorrhage (SAH), mostly occurring secondary to aneurysms, accounts for5%-10%of all strokes. Considerable advances have been made in endovascular techniques, diagnostic methods and surgical and perioperative management paradigms, but outcome for patients with SAH remains poor. Vasospasm is the leading cause for delayed neurological deficit after subarachnoid hemorrhage. Several recent clinical trials have investigated the utility of statins, endothelin-1antagonists, and magnesium sulfate. But the result are discourage. So it is emergency to search for a new drug to treat vasospasm. Valproic acid is a kind of anti-epileptic drug, which demonstrated its neuroprotection in cerebral ischemia, brain trauma, spinal cord injury and so on. Its neuroprotective effect is mediated by antioxidant and anti-inflammatory mechanism.It reminds us whether or not VPA could prevent vasospasm.Objective:To make sure whether or not valproic acid could relieve vasospasm after subarachnoid hemorrhage, and to explore the mechanism of valproic acid in preventing vasospasm after SAH.Methods:SAH model was performed using endovascular perforation technique. Adult male Sprague Dawley rats were randomly assigned into sham group, SAH+normal saline group, SAH+VPA group. Neurological deficit scores, wall thickness and luminal inner perimeter of basal artery were measure in48hours after subarachnoid hemorrhage. P-ERK1/2in basal artery tissure were measured by western blot analysis.The RNA level of proinflammation cytokines such as IL-1β, IL-6, TNF-a were measured by RT-PCR.Results:Valproic acid treatment improve neurological score, significantly increased the luminal inner perimeter and reduced the wall thickness of the BA.VPA reduced the protein level of P-ERK1/2and RNA level of proinflammatory cytokine such as IL-1β IL-6, TNF-a.Conclusion:Our preliminary study found that valproic acid could effectively alleviate vasospasm after subarachnoid hemorrhage.The underlying mechanism is that VPA can reduce protein P-ERK1/2and relieve inflammation.更多还原