不同剂量FTY720对蛛网膜下腔出血大鼠炎症因子与神经功能的影响  

Effect of Different Dosages of FTY720 on Neurologic Function and Inflammatory Factor in Rats with Subarachnoid Hemorrhage

作　　者：董晓巧[1] 俞文华[1] 杜权[1] 王昊[1] 杨定博 沈永锋[1] 江力 杜垣峰 朱强[1] DONG Xiao-qiao;YU Wen-hua;DU Quan(Department of Neurosurgery,The Hangzhou First People's Hospital(Nanjing Medical University Affiliated Hangzhou Hospital),Zhejiang 310006,China)

机构地区：[1]杭州市第一人民医院神经外科,310006

出　　处：《心脑血管病防治》2018年第2期94-97,共4页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：浙江省实验动物科技计划项目(编号:2015C37082)

摘　　要：目的揭示不同剂量FTY720对蛛网膜下腔出血大鼠神经功能的影响。方法选择健康雄性Wistar大鼠48只,随机分成假手术组、模型组、小剂量组和大剂量组,每组12只,采用枕大池两次注血建立蛛网膜下腔出血大鼠模型。假手术组和模型组大鼠予以1ml 0.9%氯化钠溶液腹腔注射,小剂量组和大剂量组大鼠按1mg/kg和5mg/kg剂量予以FTY720腹腔注射。每组6只大鼠断头处死,采用四肽荧光底物法检测海马组织caspase-3和caspase-9蛋白活性;采用酶联免疫吸附测定法检测海马组织白介素-1β、肿瘤坏死因子-α和白介素-6水平;采用Morris水迷宫实验记录每组剩余6只大鼠逃避潜伏期同时评价大鼠改良神经功能缺损程度评分。结果模型组较假手术组大鼠逃避潜伏期显著延长,改良神经功能缺损程度评分显著增高,海马组织白介素-1β、肿瘤坏死因子-α和白介素-6水平显著升高,海马组织caspase-3和caspase-9蛋白活性显著增高(均P<0.05);与模型组比较,小剂量组大鼠上述指标均显著下降(均P<0.05);与小剂量组比较,大剂量组大鼠上述指标也均显著下降(均P<0.05)。结论 FTY720可通过抑制脑炎症反应,降低神经细胞凋亡,从而改善蛛网膜下腔出血大鼠神经功能,其作用效果呈现剂量依赖性。Objective To discover the effect of different dosages of FTY720 on neurologic function in rats with subarachnoid hemorrhage.Methods A total of 48 healthy male Wistar rats were chosen and randomly assigned to sham-operation group,model group,small dosage group and big dosage group with 12 rats in each group.The rat model of subarachnoid hemorrhage was established via double autologous blood injection into cisterna magna.Rats in sham-operation group and model group were given an intraperitoneal injection of 1 ml normal saline.Rats in small dosage and big dosage groups were administrated intraperitoneally with 1 mg/kg and 5 mg/kg FTY720 respectively.6 rats were killed by decapitation in each group,interleukin-1 beta,tumor necrosis factor-alpha and interleukin-6 concentrations in hippocampus tissues were determined using enzyme linked immunosorbent assay and four peptide fluorescence substrate method was performed to investigate activities of caspase 3 and caspase 9 proteins in hippocampus tissues.Escape latency was recorded of other remaining 6 rats in each group using Morris water maze and meanwhile their modified neurological severity scores were assessed.Results As compared to sham-operation group,the escape latencies of rats were markedly prolonged,the modified neurological severity scores were obviously enhanced,the concentrations of interleukin-1beta,tumor necrosis factor-alpha and interleukin-6 in rat hippocampus tissues were obviously elevated and activities of caspase 3 and caspase 9 proteins in rat hippocampus tissues were significantly enhanced in model group(all P<0.05);when compared with model group?the preceding variables were statistically significantly decreased in small dosage group(all P<0.05);while compared to small dosage group?the above-mentioned parameters were markedly lowered in big dosage group(all P<0.05).Conclusions FTY720 might inhibit brain inflammatory reaction,depress neuronal cellular apoptosis and subsequently improve the neurologic function of rats with subarachnoid hemorrhage in a

关 键 词：FTY720 大鼠 蛛网膜下腔出血 神经功能 炎症反应 神经细胞凋亡 脑保护作用 

分 类 号：R743.3[医药卫生—神经病学与精神病学]