| 摘要: |
| 目的揭示FTY720对颅脑损伤大鼠脑保护作用的剂量疗效关系。方法将80只大鼠随机分成假手术组、模型组、小剂量组和大剂量组，每组20只，采用Feeney自由落体损伤装置建立大鼠颅脑损伤模型。小剂量组和大剂量组大鼠分别给予1、5mg/kgFTY720腹腔注射，检测每组10只大鼠外伤后24h损伤皮层凋亡神经细胞比例、Caspase-3蛋白活性和IL-1β、TNF-α及IL-6水平，记录每组剩余10只大鼠Morris水迷宫实验时逃避潜伏期、改良神经功能缺损程度评分。结果与假手术组比较，模型组大鼠逃避潜伏期明显延长（P＜0.01），改良神经功能缺损程度评分明显增高（P＜0.01），大鼠损伤皮层凋亡神经细胞比例、Caspase-3蛋白活性和IL-1β、TNF-α、IL-6水平均明显升高（均P＜0.01）；小剂量组、大剂量组较模型组大鼠上述指标均明显下降（均P＜0.01），且作用效果呈剂量依赖性。结论FTY720可能通过抑制中枢炎症反应从而减少颅脑损伤大鼠神经细胞凋亡以达到脑保护作用，且疗效呈剂量依赖性。 |
| 关键词: FTY720 大鼠 炎症反应 神经细胞凋亡 颅脑损伤 脑保护作用 |
| DOI：10.12056/j.issn.1006-2785.2017.40.8.2018-412 |
| 分类号: |
| 基金项目:浙江省实验动物科技计划项目（2014C37029） |
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| Protective effect of different dosages of FTY720 on neural function in rats with traumatic brain injury |
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Wenzhou Central Hospital
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| Abstract: |
| Objective To investigate the protective effect of different dosages of FTY720 on neural function in rats with traumatic brain injury. Methods Eighty wistar rats were randomly assigned to sham-operation group, model group, low dose group and high dose group with 20 rats in each group. Feeney free fall injury device was utilized to establish rat craniocerebral injury model. Rats in low dose group and high dose group were injected intraperitoneally with 1 or 5 mg/kg FTY720 respectively. At 24h after trauma, the apoptotic neuronal cells, activity of caspase 3 protein and concentrations of IL-1β, TNF-α and IL-6 were determined in injured cortex of 10 rats in each group. Escape latency during Morris water maze and modified neurological severity scores were recorded for remaining 10 rats in each group. Results Compared with sham-operation group, in model group, the percentages of apoptotic neuronal cells, activity of caspase 3 protein and concentrations of IL-1β, TNF-α and IL-6 in injured cortex were significantly elevated, the escape latencies of rats were markedly prolonged, and the modified neurological severity scores were significantly enhanced. The above variables were significantly decreased in low dose group and high dose group than in model group in a dose-dependent manner. Conclusion FTY720 can inhibit inflammation in central nervous
system, subsequently suppress neuronal cell apoptosis following trauma brain injury and ultimately protect brain function in a dose-dependent manner. |
| Key words: FTY720 Rat Inflammatory reaction Neuronal cell apoptosis Traumatic brain injury Brain protection |
