脊髓损伤中碱性成纤维细胞生长因子的变化与意义(英文)

Changes and significance of basic fibroblast growth factor expression after experimental spinal cord injury

背景:碱性成纤维细胞生长因子(bFGF)被认为具有神经营养作用,但有关其脊髓损伤中的变化和意义仍存在争议。目的:探索脊髓损伤时的内在自我保护修复机制,为脊髓有效治疗寻求可行性方案。设计:随机对照实验研究。地点和对象:实验在复旦大学附属中山医院中心实验室完成,雌性SD标准化大鼠55只(中科院上海实验动物中心提供)体质量200～230g。干预:采用随机数字表法将大鼠随机分为假手术对照组7只,术后1,4,7,14,21及28d组,8只/组。采用改良的Allen's法建立SD大鼠T8段脊髓损伤模型。主要观察指标:观察术后不同时期T8伤段及其远、近脊髓内的bFGF及GFAP蛋白表达分布与变化情况,组织学观察及图像处理与分析。结果:脊髓损伤后bFGF阳性表达细胞,在术后T8段及远、近段明显增多,图像分析表明,大鼠SCI后4,7,14,及21d时T8区bFGF的平均光密度,分别与对照组比较差异有显著性意义(P<0.05);而且术后14d时阳性表达最高;GFAP结果示,大量的反应性星形胶质细胞出现于创伤后脊髓灰质中,相邻切片表明,反应性星形胶质细胞是bFGF的主要阳性细胞。结论:脊髓损伤诱导了内源性bFGF蛋白表达短暂增高,提示神经营养因子bFGF可能参与SCI后的神经元营养及自我“保护”过程。

BACKGROUND:Basic fibroblast growth factor(bFGF)is known to be neurotrophic in vitro.However,the changes and effect of it in vivo after spinal cord injury(SCI) are still the subject of controversy. OBJECTIVE:To explore the self repair mechanism following SCI and find the available methods for effective treatment. DESIGN:A randomized controlled trial was conducted. SETTING and PARTICIPANTS:The experiment was completed in Central Laboratory of Zhongshan Hospital,Fudan University with 55 SD rats,weighing 200-230 g that were provided by Shanghai Laboratory Animal Center of Chinese Academy of Sciences. INTERVENTIONS:The rats were randomly divided into sham group(7 rats) and 1st,4th,7th,14th,21st and 28th day injury groups(8 rats in each group).T8 SCI model was made with improved Allen's method. MAIN OUTCOME MEASURES:The distribution and change of bFGF and GFAP protein in T8 and adjacent segments were detected in time course.And the histological observations and image analysis were performed for all sections. RESULTS:The bFGF positive cells increased obviously in T8 and adjacent segments.Image analysis showed that mean bFGF absorbance in T8 segment on the 4th,7th,14th and 21st day after injury was significantly different from that of control group respectively(P< 0.05) with the highest positive amount on the 14th day.GFAP immunoreactivity revealed that after injury,there were large number of reactive astrocytes in grey substance and they account for most of the bFGF positive cells. CONCLUSION:Injury to spinal cord induces temporal increased expression of endogenous bFGF,which suggests that FGF may play a part in neuron nutrition and self protection.