银杏二萜内酯葡胺注射液对脑缺血再灌注大鼠行为学和脑脊液成分的影响  

Effect of Ginkgo Terpene Lactones Meglumine Injection on Behavior and Cerebrospinal Fluid in Rats with Cerebral Ischemia / Reperfusion

作　　者：章晨峰[1] 曹亮[1] 邓奕[1] 李娜[1] 王振中[1] 萧伟[1] 

机构地区：[1]江苏康缘药业股份有限公司中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《中国实验方剂学杂志》2015年第20期118-122,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家"重大新药创制"科技重大专项(2013ZX09402203)

摘　　要：目的:研究银杏二萜内酯葡胺注射液及其各主要成分对脑缺血再灌注大鼠的脑保护作用和对脑脊液中氨基酸类神经递质的影响。方法:SD大鼠随机分为6组,包括正常组,模型组,银杏二萜内酯葡胺注射液组(G,20 mg·kg-1),银杏内酯B组(GB,20 mg·kg-1),银杏内酯A组(GA,20 mg·kg-1)和银杏内酯K组(GK,20 mg·kg-1)。模型组和给药组分别尾静脉注射给予生理盐水或不同药物1次后,采用线栓法制备大鼠局灶性脑缺血再灌注模型,将大鼠脑缺血再灌注后进行行为学评分并测定脑脊液中Ca2+,谷氨酸(Glu),天冬氨酸(Asp)以及磷酸肌酸激酶(CK)和乳酸脱氢酶(LDH)含量的变化。结果:与正常组比较,模型组大鼠神经缺损症状严重,脑脊液中Ca2+降低,Glu和Asp的含量显著升高,CK和LDH含量升高。与模型组比较,G及其各主要成分对脑缺血引起的行为变化有显著改善作用(P<0.05,P<0.01),能显著提高模型大鼠脑脊液Ca2+含量,并降低神经递质Glu和Asp的含量(P<0.05,P<0.01);G和GA能降低大鼠脑脊液中CK含量(P<0.05),GB能显著降低大鼠脑脊液中LDH含量(P<0.05)。结论:G及其各成分能明显改善模型动物的神经功能缺损,减少细胞外游离钙内流,降低脑脊液中兴奋性氨基酸含量,改善脑脊液生化指标的水平,对脑缺血有一定的保护作用,提示银杏二萜内酯是有效的脑保护剂。Objective： To explore the neuroprotective effects of Ginkgo terpene lactones meglumine injection（ GTLMI） and its active compounds on behavior and cerebrospinal fluid in rats with cerebral ischemia /reprerfusion injury. Method： The rats were divided into six groups which included control group,model group,GTLMI group（ G,20 mg·kg-1）,ginkgolide B group（ GB,20 mg·kg-1）,ginkgolide A group（ GA,20 mg·kg-1） and ginkgolide K group（ GK,20 mg·kg-1）. After treatment with corresponding drugs,rats in each group except control group were subjected to transient focal cerebral ischemia produced by middle cerebral artery occlusion. Neurological deficit scores and biomarkers [Ca2 ＋,glutamate（ Glu）,aspartic acid（ Asp）,lactate dehydrogenase（ LDH） and creatine phosphorinase（ CK） ] in cerebrospinal fluid were detected after ischemia /reperfusion. Result： Compared with control group, rats in model group showed severe brain damage with significant changes in cerebrospinal fluid,including decreased content of Ca2 ＋and increased levels of Glu,Asp,LDH,CK. Diterpene ginkgolides（ G,GB,GA and GK） significantly improved the animal behavior caused by cerebral ischemia after 24 h（ P〈 0. 05,P〈 0. 01）. Diterpene ginkgolides also markedly increased the content of Ca2 ＋in cerebrospinal fluid. Meanwhile,they decreased the content of neurotransmitter Glu and Asp when compared with model group（ P〈 0. 05,P〈 0. 01）. Additionally,the content of CK in cerebrospinal fluid significantly decreased in GTLMI and ginkgolide A group compared with that in model group（ P〈 0. 05）,and the content of LDH in cerebrospinal fluid significantly decreased in ginkgolide B group compared with that in model group（ P〈 0. 05）. Conclusion： GTLMI and its active components could obviously improve neurologic impairment,decrease free Ca2 ＋inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid,and improve the level of biochemical index of cerebrospinal fluid,suggestin

关 键 词：银杏二萜内酯 脑缺血再灌注 谷氨酸 天冬氨酸 钙 磷酸肌酸激酶 乳酸脱氢酶 

分 类 号：R285.5[医药卫生—中药学]