【摘要】 目的　在分子生物学水平进一步研究颅脑创伤后神经细胞延迟性死亡的机制 ,并探讨美洛宁对大鼠脑创伤后运动功能障碍的影响。方法　采用 Marm arou的方法建立大鼠重型闭合性颅脑创伤模型。将 Wistar大鼠3 0 0只随机分为脑创伤组、美洛宁治疗组、假手术组 ,每组又分别再分为伤后 3、6、12、2 4、48、72、168及 3 3 6h等 8个时相组 ,每时相组各 12只 ,剩余 12只作为正常对照组。美洛宁治疗组经致伤后 ,给予腹腔注射美洛宁〔3 0 m g/ ( kg·d)〕,直至各时相点处死 ;脑创伤组、假手术组及正常对照组在相同时间给予等量的生理盐水腹腔注射作为对照。另取 48只大鼠随机分为脑创伤组、美洛宁治疗组、假手术组及正常对照组 ,进行神经损伤严重性评分 ( NSS)测试。采用免疫组织化学、原位细胞凋亡检测及 NSS测试等方法 ,动态观察大鼠颅脑创伤后顶叶皮质的组织病理改变 ,P5 3蛋白的表达情况以及运动功能的改变。结果　脑创伤后顶叶皮质出现 P5 3蛋白表达增加并出现神经细胞凋亡及运动功能障碍。美洛宁治疗组伤后皮质神经细胞 P5 3蛋白表达高峰较创伤组明显下调 ,凋亡阳性细胞密度亦较创伤组有所下调 ,运动功能改善。结论　脑创伤后 P5 3蛋白表达增加可造成伤后神经细胞凋亡 ,伤后运动功能障碍是皮质神经细胞凋亡的必更多还原

【Abstract】 Objective This is a study on the level of molecular biology to clarify the possible mechanism of delayed neural death after traumatic brain injury(TBI) and to probe into the influences of motor function of cytidine triphosphate(CTP) on rats after brain trauma. Method The model of severe closed traumatic brain injury (TBI) was established according to the method created by Marmarou in 1994. 300 Wistar rats were divided randomly into TBI group (n=96), CTP treating group and sham operation group, and each of these three groups was divided into 8 subgroups, namely, 3, 6, 12, 24, 48, 72, 168 and 336 hours. At the same time, the rest 12 rats were taken as the normal group for comparison. The CTP treating group after injury were treated with injection of CTP (30mg/(kg·d)) in peritoneum; the TBI group, the sham operation group and the normal group were treated with normal saline for comparison at the same time and all were killed at each time point. Another 48 rats were divided randomly into 4 groups, namely, brain injury group, CTP treating group, sham operation group and the normal group, and their motor dysfuction was evaluated using Neurological Severity Score (NSS). The methods such as immunohistochemistry, TUNEL and NSS were used to dynamically observe the pathological changes in cortex of rats,the expression of P53 protein and the motor function after TBI. Results The increased expression of P53 protein and neural apoptosis showed up in cortex and motor dysfunction occurred after TBI. Conclusion The increased expression of P53 protein may bring about nerve cell apoptosis after TBI. Motor dysfunction is the inevitable outcome of nerve cell apoptosis in cortex. CTP can reduce P53 protein expression and nerve cell apoptosis, and it can improve motor function.更多还原