蛇床子素对颅脑损伤模型小鼠的神经保护作用

Protective Effects of Osthole on the Nerves of Model Mice with Craniocerebral Injury

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 improving the mice＇s neurological functions,promoting wound healing,inhibiting the production of inflammatory factors,increasing the expression of neurotrophic factors.