2022 年第 5 期 第 17 卷

塞来昔布对外伤后癫痫模型大鼠治疗作用的磁共振成像研究

Magnetic resonance imaging study on the effect of celecoxib on post-traumatic epilepsy model rats

作者：陈磊1孙雨2孙涛1郜彩斌1肖立飞1王峰3

英文作者：Chen Lei1 Sun Yu2 Sun Tao1 Gao Caibin1 Xiao Lifei1 Wang Feng3

单位：1宁夏医科大学临床医学院宁夏医科大学颅脑疾病实验室，银川750004；2宁夏医科大学颅脑疾病实验室，银川750004；3浙江大学医学院附属第一医院神经外科，杭州310003

英文单位：1School of Clinical Medicine Ningxia Medical University the Laboratory of Craniocerebral Disease of Ningxia Medical University Yinchuan 750004 China; 2the Laboratory of Craniocerebral Disease of Ningxia Medical University Yinchuan 750004 China; 3Department of Neurosurgery the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

关键词：外伤后癫痫；塞来昔布；磁共振成像

英文关键词：Post-traumaticepilepsy;Celecoxib;Magneticresonanceimaging

• 摘要：

• 目的 采用磁共振成像（MRI）方法分析塞来昔布对外伤后癫痫（PTE）模型大鼠的治疗作用。方法 将成年雄性SD大鼠21只完全随机分为模型组、治疗组及假手术组。模型组和治疗组大鼠采用右侧额叶皮质注射氯化亚铁的方法建立PTE模型，假手术组大鼠右侧额叶注射等容积0.9%氯化钠注射液。治疗组大鼠造模后2 h给予塞来昔布20 mg/（kg·d）灌胃，连续7 d同一时点给药，模型组及假手术组对应给予等容积0.9%氯化钠注射液灌胃处理。采用Racine分级评分法评价大鼠癫痫发作情况。造模后第3、7天，MRI检测大鼠脑结构及表观扩散系数（ADC）值变化情况。第7天检查结束后，取脑组织行苏木精-伊红（HE）染色和尼氏染色观察病理改变。结果 治疗组造模第3、5、6、7天Racine分级评分均低于模型组，差异均有统计学意义（均P＜0.05）。模型组及治疗组造模第3、7天MRI检查均有脑损伤表现，周边水肿带明显，但治疗组损伤及水肿程度显著减轻，假手术组内大鼠右额叶无明显损伤。造模第3天，模型组右侧额叶损伤区周围皮质ADC值低于治疗组和假手术组［(0.834±0.143)比(1.012±0.113)、(1.142±0.109)］，差异均有统计学意义（均P＜0.05）。造模第7天，模型组右侧额叶损伤区周围皮质ADC值低于假手术组，高于治疗组［(1.176±0.362)比(1.719±0.173)、（0.768±0.042）］，右海马区ADC值高于治疗组和假手术组，差异均有统计学意义（均P＜0.05）。大鼠脑损伤区周围皮质HE染色观察结果显示，模型组损伤最严重，可见细胞数目减少、间隙增加，排列紊乱，胞质水肿变性；右侧海马区尼氏染色显示模型组细胞数目明显少于其他2组。结论  MRI检查证实塞来昔布可显著改善PTE模型大鼠的脑损伤，降低癫痫发作级别。

• Objective  To analyze the effect of celecoxib on post-traumatic epilepsy (PTE) model rats by magnetic resonance imaging (MRI). Methods Totally 21 adult male SD rats were randomly divided into model group, treatment group and sham operation group. The rats in model group and treatment group were injected with ferrous chloride into the right frontal cortex to establish the PTE model. The rats in sham operation group were injected with equal volume of 0.9% sodium chloride injection into the right frontal lobe. The rats in treatment group were given celecoxib 20 mg/(kg·d) by gavage 2 h after modeling, and the administration was given at the same time point for 7 d. The rats in model group and sham operation group were given equal volume of 0.9% sodium chloride injection by gavage. Racine grade was used to evaluate the seizure of epilepsy in rats. On the 3rd and 7th days after modeling, the changes of brain structure and apparent diffusion coefficient (ADC) were detected by MRI. After the examination on the 7th day, the brain tissue was taken for hematoxylin and eosin (HE) staining and Nissl staining to observe pathological changes. Results  The Racine grade of the treatment group was lower than that of the model group on the 3rd day and 5th-7th days (all P＜0.05). Both the model group and the treatment group showed brain injury on the 3rd and 7th days of modeling, the peripheral edema zone was obvious, but the injury and edema degree in the treatment group were significantly reduced, and there was no obvious injury to the right frontal lobe in the sham operation group. On the 3rd day of modeling, the ADC value of cortex around the right frontal lobe injured area in the model group was lower than that in the treatment group and sham operation group［(0.834±0.143) vs (1.012±0.113), (1.142±0.109)］(both P＜0.05). On the 7th day of modeling, the ADC value of cortex around the right frontal lobe injured area in the model group was lower than that in the sham operation group and higher than that in the treatment group［(1.176±0.362) vs (1.719±0.173), (0.768±0.042)］, and the ADC value of right hippocampus in the model group was higher than that in the treatment group and sham operation group (all P＜0.05). HE staining of the cortex around the brain injury area of rats showed that the model group was the most seriously injured, with decreased cell number, increased gap, disordered arrangement, cytoplasmic edema and degeneration; Nissl staining in the right hippocampus showed that the number of cells in the model group was less than that in the other groups. Conclusion MRI confirms that celecoxib can significantly alleviatethe brain damage of the PTE model rats and reduce the seizure level of epilepsy.