柴胡细辛汤加减对颅脑损伤模型大鼠海马CA1区BDNF、SYN1表达与超微结构的影响  

Effect of Modified Chaihu Xixin Decoction (柴胡细辛汤) on Expression of BDNF and SYN1 and Ultrastructure of Hippocampal CA1 in Rats with Craniocerebral Injury

作　　者：张国梁[1,2] 周承扬[2] 庞坚[1] 石瑛[1] 赵咏芳[1] 詹红生[1] 石印玉[1] 

机构地区：[1]上海中医药大学附属曙光医院 [2]上海市闸北区中心医院

出　　处：《中医杂志》2017年第8期682-687,共6页Journal of Traditional Chinese Medicine

基　　金：教育部国家重点学科(100508);上海市中医药领军人才建设项目(沪卫中医[2012]63号);上海领军人才"地方队"培养计划(沪人社专领[2010]081号);上海市进一步加快中医药事业发展三年行动计划(2014年-2016)项目(ZY3-JSFC-1-1025;ZY3-CCCX-1-1003);上海市"杏林新星"计划(ZYSNXD011-RC-XLXX-20130050);上海市卫生局中医药科研基金项目(2012QL002A);上海市闸北区卫生科研课题(2012ZY01)

摘　　要：目的观察柴胡细辛汤加减对颅脑损伤模型大鼠认知功能和神经功能缺损的作用及其可能机制。方法将89只SD大鼠随机分为假手术组16只,模型组、阳性对照组和中药低剂量组各18只,中药高剂量组19只,除假手术组外其余各组建立控制性皮层冲击损伤模型。造模次日阳性对照组予安理申片0.45 g/(kg·d),中药低、高剂量组分别给予柴胡细辛汤加减方6.5、13 g生药/(kg·d),假手术组、模型组予等体积双蒸水,各组灌胃4周。比较各组大鼠认知功能(水迷宫测试)、神经功能缺损评分(m NSS)、脑组织病理与海马CA1区超微结构,并检测CA1区脑源性神经生长因子(BDNF)、突触素1(SYN1)蛋白表达。结果各组在造模后0、3、7天时m NSS评分较假手术组均明显升高(P<0.01),中药高剂量组在第7、28天时m NSS评分较模型组降低,中药低剂量组在28天时亦低于模型组(P<0.05或P<0.01)。水迷宫测试中,各给药组逃避潜伏期时间较模型组减少(P<0.05或P<0.01)。各给药组损伤海马区病理形态学显示优于模型组,中药高、低剂量组能够改善海马CA1区受损的神经元、线粒体和突触的超微结构。中药高剂量组BDNF表达明显高于模型组和阳性对照组,中药高剂量组SYN1表达高于模型组(P<0.01)。结论柴胡细辛汤加减能够改善颅脑损伤模型大鼠认知功能及其神经功能缺损,其机制可能是提高海马CA1区BDNF、SYN1的表达以促进损伤的神经元修复与突触重塑,改善海马CA1区超微结构。Objective To observe the effect of modified Chaihu Xixin Decoction（ 柴胡细辛汤） on the cognitive function and neurological function impairment in rats with craniocerebral injury and the possible mechanism. Methods Eighty nine Sprague Dawley rats were randomly divided into sham operation group（ n = 16）,model group（ n = 18）,positive control group（ n = 18） and low dose（ n = 18） and high dose（ n = 19） of Chinese herb groups. Controlled cortical impact injury model were built in these groups except sham operation group. The day after modeling,positive control group was given 0. 45 g/（ kg·d） of Donepezil Hydrochloride Tablets,low dose of Chinese herb group was given 6. 5 g/（ kg·d） of modified Chaihu Xixin Decoction,high dose of Chinese herb group was given 13 g/（ kg·d） of Chaihu Xixin Decoction,and sham operation group and model group were given double distilled water of the same volume. Each group was treated for 4 weeks by gavage. Cognitive function（ water maze test）,modified neurological severity score（ m NSS）,brain histopathology and ultrastructure of hippocampal CA1 in these groups were compared.The expression of brain derived neurotrophic factor（ BDNF） and synaptophysin1（ SYN1） were tested. Results On day 0,day 3,and day 7 after modeling,m NSS in the all other groups were significantly increased compared with that in the sham operation group（ P 〈0. 01）. On day 7 and day 28 after modeling,m NSS in the high dose of Chinese herb group was decreased compared with that in model group. At day 28 after modeling,m NSS in the low dose of Chinese herb group was also decreased compared with that in model group（ P〈 0. 05 or P 〈0. 01）. In water maze test,escape latency time in groups given medicines was decreased compared with that in model group（ P 〈0. 05 or P 〈0. 01）. Injured hippocampal pathologic examination in groups given medicines was better than that in model group.The injured ultrastructure of neuron,mitochondrion and synapse in hippoca

关 键 词：颅脑损伤 柴胡细辛汤 认知功能 脑源性神经营养因子 突触素1 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]