吗替麦考酚酯对弥漫性轴索损伤大鼠海马胶质瘢痕形成及学习记忆功能的影响  

Effect of mycophenolate mofetilglial on glial scar formation into the hippocampus and learning and memory functions of the rats with diffuse axonal injury

作　　者：尹义国 孙兆良 陈二涛[1] 冯东福[1] 

机构地区：[1]上海交通大学医学院附属第三人民医院神经外科,上海交通大学医学院创伤医学研究所,201900

出　　处：《中华创伤杂志》2015年第10期949-953,共5页Chinese Journal of Trauma

基　　金：国家自然科学基金资助项目（81372047）;上海市科委基金资助项目（124119a1600）

摘　　要：目的探讨吗替麦考酚酯（MMF）对弥漫性轴索损伤（DAI）大鼠海马区胶质瘢痕形成及学习记忆功能的影响。方法将96只成年SD大鼠按随机数字表法分为空白对照组、等渗盐水（NS）组和MMF组，每组32只。免疫组化染色检测DAI后大鼠海马区活化小胶质细胞、活化星形胶质细胞以及硫酸软骨素蛋白聚糖（CSPGs）的表达，Image—Pro Plus软件定量评估DAI易损区星形胶质细胞、小胶质细胞、CSPGs的表达量。Morris水迷宫试验检测各组大鼠伤后7～11d、28～32d学习记忆功能。对各组伤后7，14，28d胶质瘢痕主要成分累积吸光度（伪）值及伤后7～11d、28—32d的Morris水迷宫参数进行统计分析，并对两者进行相关性分析。结果在各时相点，MMF组大鼠海马区胶质瘢痕主要成分伪值均低于NS组与空白对照组（P〈0．05）；在伤后7～11d，各组大鼠Morris水迷宫参数（目标象限路程百分比和时间百分比）的差异无统计学意义且无任何相关性；在伤后28—32d，MMF组大鼠Morris水迷宫参数（目标象限路程百分比和时间百分比）明显降低（P〈0．01）；伤后28d胶质瘢痕的主要成分M值与DAI大鼠28—32d Morris水迷宫参数的平均速度和逃匿潜伏期呈正相关关系，与目标象限停留路程百分比和停留时间百分比呈负相关关系（P〈0．01）。结论早期应用MMF能够显著抑制DAI大鼠海马区胶质瘢痕形成，改善DAI大鼠恢复期的学习记忆功能。Objective To determine the intervention of mycophenolate mofetil （MMF） in glial scar formation and learning and memory function in a rat model of diffuse axonal injury （DAI）. Methods Ninety-six SD rats were randomly divided into sham group, normal saline （NS） group and mycophenolate mofetil （MMF） group according to the random number table, with 32 rats per group. Immunohistochemistry was used to detect activated microglia cells, activated astrocytes and chondroitin sulphate proteog[ycanns （CSPGs） in the hippocampus. Image-Pro Plus software was used to quantitatively assess the changes of activated microglia cells, activated astrocytes and CSPGs. Morris water maze was applied for testing rat learning and memory function. Integrated absorbance （ IA ） of major constituents （microglia, astrosyte, chondroitin sulphate proteoglycan） of the glial scar was determined and analyzed for the correlation with the parameters of MWM. Results At 7, 14 and 28 days after injury, MMF group showed decreased IA of activated microglia in the hippocampus compared to sham and NS groups （ P 〈 0. 05 ）. At 7-11 days after injury, percent distance and percent time in the target quadrant of Morris water maze did not differ significantly among the three groups and were not related to the IA of glial scar. At 28-32 days after injury, percent distance and percent time in the target quadrant of Morris water maze lowered significantly in MMF group. At 28 days after injury, IA of the glial scar had a positive correlation with mean speed and mean escape latency, but negative correlation with percent distance and time in the target quadrant that measured in Morris water maze at 28-32 days after injury. Conclusion MMF significantly attenuates glial scar formation into the hippocampus and improves learning and memory function in rats during the recovery stage when administered in the early stage after DAI.

关 键 词：弥漫性轴索损伤 海马 吗替麦考酚酯 

分 类 号：R651.15[医药卫生—外科学]