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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Western blot法检测NF-κB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-κB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。
Objective To investigate the effect and mechanism of FTY720 on neurological function in rats with subarachnoid hemorrhage. Methods Ninety-six rats were randomly divided into normal group, sham operation group, model group and treatment group, with 24 rats in each group. Subarachnoid hemorrhage rat model was established by double injection of occipital cistern. The treatment group by intraperitoneal injection of 1mg / kg FTY720, the other three groups were injected intraperitoneally 0.9ml sodium chloride solution 1ml. 24h later, 12 rats in each group were sacrificed and the hippocampus was separated. The expression of NF-κB protein was detected by Western blot. The expression of OX-42 protein in microglia was detected by immunohistochemical staining. Twelve rats in each group For neurological assessment. Results The expression of NF-κB in hippocampus and the expression of OX-42 in microglia in model group were significantly higher than those in normal group and sham-operated group (all P <0.05) <0.05). Compared with the model group, the treatment group dropped significantly (P <0.05) at 7, 14, 21 and 28 days after the forearm placement of experimental score, balance experimental score and improvement of neurological deficit score. Conclusion FTY720 can improve the neurological function in rats with subarachnoid hemorrhage. Its mechanism may be related to the central inflammation inhibition of FTY720.