Necrostatin-1对蛛网膜下腔出血后皮层细胞坏死状凋亡、坏死与自噬的影响  

Effect of necrostatin-1on cortical necroptosis,necrosis and autophagy after subarachnoid hemorrhage

作　　者：张斌飞[1] 安吉洋[1] 宋锦宁[1] 张明[1] 罗显华[1] 黄廷钦[1] 翟海程[1] 白立曦[1] 

机构地区：[1]西安交通大学医学院第一附属医院神经外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2013年第6期740-743,753,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.30870844);陕西省"13115"重大科技创新专项基金资助项目(No.2008ZDKG-66);教育部高等学校博士学科点专项科研基金资助项目(No.20110201110060)~~

摘　　要：目的研究necrostatin-1对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后皮层细胞坏死状凋亡、自噬与坏死调节的作用。方法 72只SD大鼠随机分成假手术组、模型组、赋形剂组、necrostatin-1组。赋形剂组经侧脑室给予二甲基亚砜2μL,necrostatin-1组给予necrostatin-1 5.2μg溶于2μL二甲基亚砜。血管内穿刺法制作SAH模型。每组9只观察皮质受体相互作用蛋白3和微管相关蛋白1轻链3的变化,检测坏死状凋亡与自噬;9只腹腔注射碘化丙啶观察细胞坏死。对所有大鼠进行6、12、24hLoeffler神经行为学评分。结果 Necrostatin-1下调皮质受体相互作用蛋白3和微管相关蛋白1轻链3的表达(P<0.05),减少皮层碘化丙啶阳性细胞数目(P<0.05),提高12、24h的Loeffler神经功能评分(P<0.05),有改善SAH预后的作用。结论 Necrostatin-1可能在抑制SAH后脑细胞坏死状凋亡时也下调了自噬与坏死水平。Objective To explore after subarachnoid hemorrhage （SAH） the effects of necrostatin-1 on cortical necroptosis, autophagy and necrosis Methods Totally 72 SD rats were randomly divided into sham operation group, model group, vehicle group and necrostatin-1 group. Rats in vehicle group were given 2 #L of dimethyl sulfoxide by intracerebroventricular injection while those in necrostatin-1 group were given 5.2 ~tg of necrostatin-1 dissolved in 2 ~tL of dimethyl sulfoxide. Subarachnoid hemorrhage models were induced by intravascular puncture. In each group 9 rats were used to observe the expressions of receptor interacting protein 3 and microtubule associated protein 1 light chain 3 in the cerebral cortex by Western blot; 9 rats were injected intraperitoneally with propidium iodide to observe necrosis in each group. Loeffler neurological score was recorded for all rats at 6, 12 and 24 h. Results Necrostatin-1 suppressed receptor interacting protein 3 and microtubule associated protein 1 light chain 3 in the cerebral cortex （P^0.05）, decreased the number of propidium iodide positive cells in the cortex （P^0.05）, and improved Loeffler neurological scores at 12 and 24 h （P^0.05）, which showed that necrostatin-1 could improve the prognosis after SAH. Conclusion Necrostatin-1 might suppress the level of autophagy and necrosis when inhibiting post-SAH necroptosis in cerebral cells.

关 键 词：necrostatin-1 蛛网膜下腔出血 坏死状凋亡 坏死 自噬 脑皮质细胞 大鼠 

分 类 号：R743.35[医药卫生—神经病学与精神病学]