硫辛酸胺在实验性蛛网膜下腔出血早期脑损伤中的神经保护作用及相关机制的实验分析-神经外科专业论文.docxVIP

II II 中文摘要 硫辛酸胺在实验性蛛网膜下腔出血早期脑损伤中的神经保护作用及相关机制的实验研究 blue EB）来评价出血后的血脑屏障（blood–brain barrier BBB）的通透性，末端标记 法（terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling TUNEL）染 色测定神经细胞的凋亡，相关的试剂盒来测定新鲜脑组织中氧化应激指标。 结果：实验 1：72 小时后，通过比较各组之间的荧光强度，得出 SAH 组中 LAMP-1 在神经元细胞质中的表达较假手术组显著减弱，与 LA 组相比，LAMP-1 在 LAP (100 mg/kg)组中荧光强度最强；但在星型胶质细胞中，我们发现假手术组，SAH 组和干 预组之间的荧光强度无明显差异。因次，我们选择 LAP (100 mg/kg)，LAP (150 mg/kg) 两个剂量行第二部分的实验。实验 2：72 小时后，与假手术组相比，我们观察到 Cathepsin B/D，caspase-3，Bax，ferritin 和 HO-1 在脑组织中表达水平显著上调，LA， LAP 不仅能显著抑制上述蛋白的表达，同时大鼠神经功能缺陷，脑水肿含量，血脑 屏障通透性，铁沉积，皮层细胞的凋亡率和氧化应激指标都得到了明显的改善，值得 注意的是，高剂量 LAP 神经保护效果最佳。 结论：LAP 在实验性 SAH 后 EBI 中可以靶向作用于溶酶体内铁，稳定溶酶体膜， 抑制 Cathepsins 的释放，阻断 Cathepsins 介导的凋亡通路发挥神经保护作用。 关键词：硫辛酸胺; 蛛网膜下腔出血; 组织蛋白酶; 溶酶体内铁，溶酶体膜通透 性 作 者：汪 洋 指导老师：虞正权 主任医师 PAGE IV PAGE IV 硫辛酸胺在实验性蛛网膜下腔出血早期脑损伤中的神经保护作用及相关机制的实验研究 英文摘要 Experimental research of the neuroprotection of α-lipoic acid-plus and the relevant neuroprotective mechanism on early brain injury following experimental subarachnoid hemorrhage in rats Abstract objective: As a natural antioxidant, α-lipoic acid (LA) has been shown to play neuroprotective effects on subarachnoid hemorrhage (SAH). α-lipoic acid-plus (LAP), an amine derivative of LA, could protect cells against oxidant challenges via interacting with intralysosomal iron. However, whether LAP could inhibit the early brain injury (EBI) after SAH and the underlying mechanisms were still not well known. This study was designed to evaluate the potential protective effects of LA and LAP on the EBI and the underlying mechanisms in a rat model of SAH. Methods: In experiment 1, 42 Sprague-Dawley (SD) rats were randomly divided into 7 groups of 6 rats each: sham group, SAH + vehicle group, SAH + LA (100 mg/kg) group, SAH + LAP (50 mg/kg) group, SAH + LAP (100 mg/kg) group, SAH + LAP (150 mg/kg), and SAH + LAP (200 mg/kg). LAP was synthesized by LA, Either LA or LAP was administered through an orogastric tube at 4 h after the induction of SAH and continued