脑缺血再灌注后白质损伤研究  

Experimental Study of White Matter Damage after Cerebral Ischemia

作　　者：高晓玉[1] 王得新[2] 张拥波[2] 

机构地区：[1]山东烟台毓璜顶医院神经内科,山东烟台264000 [2]首都医科大学附属北京友谊医院神经内科,北京100050

出　　处：《中国神经免疫学和神经病学杂志》2009年第3期183-186,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(30570626)

摘　　要：目的观察大鼠脑缺血再灌注后不同时间髓鞘和轴突损伤的病理变化,明确脑缺血后白质损伤情况。方法利用线栓法制备雄性SD大鼠大脑中动脉闭塞(MCAO)模型。将大鼠随机分为假手术组和缺血2 h再灌注6 h、12 h、1 d、3 d、7 d、14 d和21 d组,每组4只。于规定时间点处死大鼠取脑,行常规HE染色观察皮层区神经元病理变化,行Luxol fast blue-periodic acid Schiff(LFB-PAS)染色法标记大脑神经髓鞘,Bielschowsky银染法标记轴突,计算缺血侧与健侧髓鞘染色的积分吸光度(integrated optical densities,IODs)比值代表白质受损程度。结果MCAO再灌注6 h皮层区即已出现细胞间质水肿,核深染、固缩,细胞变性坏死。随再灌注时间延长损伤加重,神经元进一步减少。再灌注14 d及21 d有大量胶质细胞增生。与假手术组比较,再灌注6 h时髓鞘染色IODs比值亦开始下降(P<0.01);12 h时有空洞形成,再灌注14 d髓鞘损伤达高峰,IODs比值降到最低,髓鞘脱失明显;21 d时髓鞘IODs比值与14 d比较差异无统计学意义(P>0.05)。轴突变化规律与髓鞘基本相同。结论脑白质对缺血同样敏感,在急性脑缺血早期即已存在白质损伤,并随再灌注时间延长逐渐加重,提示脑缺血后应及早对白质损伤进行干预。Objective To observe the pathological change of the myelin sheath and axon at different time points after focal cerebral ischemia and reperfusion in rats, and to identify the white matter damage after ischemia. Methods Sprague-Dawley male rats were subjected to 2 hours of middle cerebral artery occlusion （MCAO） by an intraluminal thread. All the rats were divided into reperfusion 6 h, 12 h, 1 d, 3 d, 7 d,14 d, 21 d groups and sham-operation group （n=4）. HE staining was used to observe the histopathology of gray matter. Myelin sheath was characterized by Luxol fast blue-periodic acid Schiff Staining （LFB-PAS）, and axon was stained by Bielschowsky silver staining. The integrated optical densities （IODs） were measured after dyeing by LFB-PAS in the external capsule of both hemispheres, and the IODs ratio was calculated to reflect the severity of white matter damage. Results There were intercellular substance edema, stained nucleus pyknosis and cell necrosis at 6h after ischemic reperfusion. The number of local neurons gradually reduced, and a lot of proliferated glial cells were observed at 14 d and 21 d after ischemia. Myelin sheaths lost their LFB-PAS stabilization and IODs ratio decreased at 6 h after ischemia-reperfusion （P〈0.01 vs sham-operation group）. It appeared as empty spaces （vacuoles） separating myelin sheaths at 12 h. The IODs ratio decreased gradually and became its lowest level at 14 d. There were no significant differences in IODs ratio between 14 d group and 21 d group （P〉0.05）. The pathologic change of axons was similar to that of Myelin sheaths. Conclusions The white matter damage was observed in the early stage of brain ischemia-reperfusion and became worse over time, which suggests cerebral white matter is as sensitive as gray matter to ischemic injury, and it is important to protect white matter after cerebral ischemia.

关 键 词：脑缺血 白质损伤 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]