文章摘要
王梓,邢宏义.氨甲酰促红细胞生成素促进脑缺血后神经再生的实验研究[J].中华物理医学与康复杂志,2017,39(4):247-252
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氨甲酰促红细胞生成素促进脑缺血后神经再生的实验研究
  
DOI:
中文关键词: 脑缺血  氨甲酰促红细胞生成素  生长相关蛋白-43  半胱氨酸蛋白酶-3  神经再生
英文关键词: Cerebral ischemia  Carbamylated erythropoietin  Growth-associated protein 43  Caspase-3  Neural regeneration
基金项目:湖北省自然科学基金(2016CFB626)
作者单位
王梓,邢宏义 430022武汉华中科技大学同济医学院附属协和医院神经内科 
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中文摘要:
      目的观察氨甲酰促红细胞生成素(CEPO)对实验大鼠脑缺血后LINGO-1、生长相关蛋白(GAP-43)表达及脑梗死体积的影响,探讨CEPO对脑缺血后神经再生的促进作用。 方法将48只SD大鼠分为假手术组、缺血对照组及氨甲酰促红细胞生成素治疗组(简称CEPO治疗组),采用线栓法将缺血对照组、CEPO治疗组大鼠制成大脑中动脉闭塞(MCAO)模型。各组大鼠于脑缺血90min后拔出线栓,CEPO治疗组同时注射0.5ml CEPO,缺血对照组及假手术组均注射0.5ml生理盐水。于缺血再灌注第7天时处死各组大鼠,采用免疫印迹技术检测LINGO-1和活化型caspase-3表达;采用免疫组化染色技术检测GAP-43表达;采用甲酚紫染色法检测各组大鼠脑梗死体积及脑水肿情况。 结果假手术组、缺血对照组及CEPO治疗组LINGO-1表达值分别为(0.25±0.02)、(1.22±0.06)和(0.66±0.05),各组间差异均具有统计学意义(P<0.05)。假手术组大鼠脑皮质未见活化型caspase-3表达,缺血对照组缺血脑皮质活化型caspase-3表达值上升至(86.6±10.2)%,CEPO治疗组则下降至(40.3±8.7)%,各组间差异均具有统计学意义(P<0.05)。假手术组、缺血对照组及CEPO治疗组GAP-43阳性表达值分别为0、(55.02±1.62)个/HP和(72.11±3.23)个/HP,各组间差异均具有统计学意义(P<0.05)。另外CEPO治疗组脑梗死体积及脑水肿程度均显著小于缺血对照组(P<0.05)。 结论脑缺血后给予CEPO干预能抑制实验大鼠脑梗死部位LINGO-1及活化型caspase-3表达、促进GAP-43蛋白表达、减小脑梗死体积及脑水肿程度,从而发挥促神经再生作用。
英文摘要:
      Objective To investigate any effects of carbamylated erythropoietin (CEPO) on the expression of LINGO-1, growth-associated protein-43 (GAP-43) and the infarcted volume after cerebral ischemia, so as to explore the effect of CEPO on neural regeneration after cerebral ischemia. MethodsForty-eight Sprague-Dawley rats were randomly divided into a sham operation group, an ischemia control group and a CEPO treatment group, each of 16. Middle cerebral artery occlusion (MCAO) was used to simulate focal cerebral ischemia in all except the rats in the sham operation group. Then the CEPO group was injected with 0.5 ml of CEPO, while the other two groups were given a 0.5 ml injection of normal saline daily for 7 days before they were sacrificed to prepare slices of brain tissue. Western blotting was used to detect the expression of LINGO-1 and activated caspase-3. Immunohistochemical staining was applied to observe the expression of GAP-43. The slices of brain tissue were stained with cresyl violet and the volume of infarction and edema were quantified with the Image J software. ResultsThe average expression of LINGO-1 in the sham operation group, the ischemia control group and the CEPO treatment group were (0.25±0.02), (1.22±0.06) and (0.66±0.05) respectively, with significant differences among the 3 groups. There was no expression of activated caspase-3 in the sham operation group. However, the expression of activated caspase-3 increased significantly (to 86.6±10.2)% in the ischemia control group and increased significantly less (to 40.3±8.7)% in the CEPO treatment group. The average positive expression of GAP-43 in the sham operation group, the ischemia control group and the CEPO treatment group were 0, (55.02±1.62) and (72.11±3.23)/HP, respectively, with significant differences among them. Moreover, the average volumes of cerebral infarction and brain edema in the CEPO treatment group were significantly lower than those in the ischemia control group. ConclusionsCEPO can inhibit the expression of LINGO-1 and activated caspase-3, promote the expression of GAP-43, reduce infarct volume and limit cerebral edema so as to promote neural regeneration after cerebral ischemia, at least in rats.
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