目的:研究蛇床子素对颅脑损伤模型小鼠的神经保护作用。方法:开颅钻孔以复制小鼠颅脑损伤模型。实验分为假手术(等容蒸馏水)组、模型(等容蒸馏水)组和蛇床子素高、中、低剂量(30、20、10 mg/kg)组,复制模型成功1 h后ip给药,每天1次,连续14 d。在复制模型12 h与3、7、14、21 d后对小鼠进行神经功能缺损评分;在复制模型7、14 d后进行HE染色,显微镜下观察脑组织损伤面积;在复制模型24、72 h后测定小鼠脑组织中髓过氧化物酶(MPO)活性;在复制模型7 d后,采用免疫组化法测定小鼠脑组织匀浆中脑源神经生长因子(BDNF)、神经营养因子(NT)3的表达。结果:复制模型成功3、14、21 d后,蛇床子素高、中剂量组小鼠神经功能缺损评分降低;复制模型成功7 d后,蛇床子素高剂量组小鼠神经功能缺损评分降低。复制模型成功7 d后,蛇床子素高剂量组小鼠脑组织损伤面积减小;复制模型成功14 d后,蛇床子素高、中剂量组小鼠脑组织损伤面积减小。复制模型成功24、72 h后,蛇床子素高剂量组小鼠脑组织中MPO活性减弱。复制模型成功7 d后,蛇床子素高、中剂量组小鼠脑组织中BDNF、NT-3表达增强。以上差异均有统计学意义(P〈0.01或P〈0.05)。结论:蛇床子素对颅脑损伤模型小鼠神经具有一定保护作用,其机制为改善小鼠神经功能、促进伤口愈合,抑制炎症因子的产生及促进神经营养因子表达。
OBJECTIVE:To investigate the protective effects of osthole on the nerves in model mice with craniocerebral injury.METHODS:Mice models of craniocerebral injury were established by craniotomy drill.There was a sham-operation group(isometric normal saline),a model group(isometric normal saline) and osthole high,mediu,low dose groups(30,20,10 mg/kg).The drugs were given to the mice 1 h after successful establishment of the models,ip,once a day,for consecutive 14 d.Neurological severity score was conducted for the mice 12 h,3 d,7 d,14 d and 21 d after the establishment of models;HE stain was conducted 7 d and 14 d thereafter and the wounds areas of brain were observed by microscope;the activity of myeloperoxidase(MPO)in the homogenate of mice's brain tissues were determined 1 d and 3 d after the establishment of models;immunohistochemical method was adopted to determine the expressions of the brain-derived neurotrophic factors(BDNF)and neurotrophic factor(NT)3 in the mice's brain tissues 7 d after the establishment of models.RESULTS:Compared with model group,the neurological severity scores of the mice in osthole high dose group and medium dose group were decreased 3 d,14 d and 21 d after the establishment of models;that in osthole high dose group were decreased 7 d after the establishment of models.The wounds areas of brain in osthole high dose group were smaller 7 d after the establishment of models;those in osthole high dose group and medium dose group were smaller 14 d after the establishment of models.The activity of MPO in the brain tissue in osthole high dose group was decreased 24 h and 72 h after the establishment of models.The expressions of the BDNF and NT-3 in the brain tissue homogenate in osthole high dose group and medium dose group were increased 7 d after the establishment of models,with significant differences(P〈0.01 or P〈0.05).CONCLUSIONS:Osthole has certain protective effects on the nerves in mice with craniocerebral injury.The mechanism may be related to