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FTY720对蛛网膜下腔出血大鼠神经功能的作用及机制 |
董晓巧, 俞文华, 杜权, 王昊, 杨定博, 沈永锋, 江力, 胡强, 杜垣锋, 朱强, 车志豪, 孙承龙, 刘群杰, 王鼎
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杭州市第一人民医院
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摘要: |
目的探讨FTY720对蛛网膜下腔出血大鼠神经功能的作用及相关机制。方法将96只大鼠随机分成正常组、假手术组、模型组和治疗组,每组24只,采用枕大池二次注血建立蛛网膜下腔出血大鼠模型。治疗组按1mg/kg腹腔注射FTY720,其他3组腹腔注射0.9%氯化钠溶液1ml。24h后每组取12只断头处死并分离海马组织,采用Westernblot法检测NF-资B蛋白表达,采用免疫组化染色法检测小胶质细胞OX-42蛋白表达;每组剩余12只大鼠用于神经功能评估。结果模型组大鼠海马组织NF-资B蛋白表达水平、小胶质细胞OX-42蛋白表达水平均较正常组、假手术组明显增加(均P<0.05),治疗组较模型组明显减少(P<0.05)。前肢放置实验评分、平衡实验评分和改良神经功能缺损程度评分术后7、14、21、28d比较,治疗组较模型组均明显下降(均P<0.05)。结论FTY720可改善蛛网膜下腔出血大鼠神经功能,其作用机制可能与FTY720的中枢炎症抑制作用有关。 |
关键词: FTY720 大鼠 蛛网膜下腔出血 神经功能 炎症反应 脑保护作用 |
DOI:10.12056/j.issn.1006-2785.2017.39.18.2016-1373 |
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基金项目:浙江省实验动物科技计划项目(2015C37082) |
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Effect of FTY720 on neurological function in rats with subarachnoid hemorrhage and related mechanism |
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Hangzhou First People's Hospital
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Abstract: |
Objective To investigate the effect of FTY720 on neurological function in rats with subarachnoid hemorrhage (SAH) and the related mechanism. Methods A total of 96 rats were randomly assigned to normal group, sham-operation group, model group and treatment group with 24 rats in each group. The rat SAH model was established via autologous blood injection into cisterna magna. Rats in treatment group were given intraperitoneally with 1mg/kg FTY720. Rats in other three groups were given intraperitoneal injection of 1ml normal saline. After 24 hours, 12 rats in each group were sacrificed by decapitation and their
hippocampus tissue samples were collected. Western blot was used to determine the expression of nuclear factor-kappa B (NF-资B). Immunohistochemistry was utilized to investigate the microglial OX-42 expression. Other 12 rats in each group experienced neurological function assessment. Results The relative expressions of NF-资B and microglial OX-42 in the
hippocampus tissues were significantly higher in model group than those in normal group and sham-operation group (all P< 0.05), also higher than those in treatment group (all P<0.05). Forelimb-placement test, balance test and modified neurological severity scores at d 7, 14, 21 and 28 postoperatively in treatment group were all significantly lower than those in model group (all P<0.05). Conclusion FTY720 can markedly improve the neurological function of rats with SAH, which may be related to the inhibition of inflammation in central nervous system. |
Key words: FTY720 Rat Subarachnoid hemorrhage Neurological function Inflammation Cerebral protective effect |