中国中药杂志

2017, v.42(24) 4733-4737

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银杏二萜内酯葡胺注射液对大鼠局灶性脑缺血的保护作用
Protective effects of Ginkgo Terpene Lactones Meglumine Injection on focal cerebral ischemia in rats

罗燕平;张红;胡晗绯;曹泽彧;张新庄;曹亮;王振中;萧伟;
LUO Yan-ping;ZHANG Hong;HU Han-fei;CAO Ze-yu;ZHANG Xin-zhuang;CAO Liang;WANG Zhen-zhong;XIAO Wei;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Jiangsu Kanion Parmaceutical Co.,Ltd.;

摘要(Abstract):

探讨银杏二萜内酯葡胺注射液对大鼠局灶性脑缺血再灌注损伤(MCAO)的保护作用,并探讨其可能的作用机制。雄性SD大鼠140只,随机分为假手术组、模型组、银杏提取物注射液(金纳多,1.0 m L·kg~(-1))、尼莫地平注射液(0.2 mg·kg~(-1))组、银杏二萜内酯葡胺注射液(5.2,2.6,1.3 mg·kg~(-1))组;所有动物手术前4 d尾静脉注射给药(模型组及假手术组给予生理盐水)。除假手术组,其他动物通过右侧大脑中动脉线栓塞法(MCAO)制作局灶性脑缺血再灌注模型。缺血3 h后,所用动物再次尾静脉注射给药。大鼠缺血再灌注后进行神经行为学评分并采用TTC染色法观察脑组织梗死率;测定脑组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)、乳酸(LA)含量及脑脊液中Ca~(2+),谷氨酸(Glu),天冬氨酸(Asp)以及磷酸肌酸激酶(CK-BB)和乳酸脱氢酶(LDH)含量的变化。与假手术组相比,模型组大鼠脑梗死率显著增加,神经严重缺损;脑组织匀浆中MDA、LA含量升高,GSH、SOD含量降低;脑脊液中Ca~(2+)浓度降低,Glu和Asp的含量及CK-BB、LDH含量显著升高。与模型组相比,银杏二萜内酯葡胺注射液高、中剂量组能显著减少脑梗死率,改善脑神经功能缺损症状;提高SOD、GSH活性,减少血清中MDA、LA含量;升高脑脊液中Ca~(2+)浓度,减低神经递质Glu和Asp的含量及CK-BB、LDH的含量。银杏二萜内酯葡胺注射液能明显改善模型动物的神经功能缺损,其机制可能与修复血脑屏障,减少自由基,减少细胞外游离钙内流,降低脑脊液中兴奋性氨基酸含量等有关,从而保护脑缺血。
To investigate the protective effects of ginkgo diterpene lactone meglumine injection(GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion( MCAO) in rats,and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group,model group,ginkgo biloba extract injection( Ginaton,1. 0 m L·kg~(-1)) group,nimodipine(0. 4 mg·kg~(-1)) group,and GDLMI(5. 2,2. 6,1. 3 mg·kg~(-1)) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation( normal saline in model group and sham operation group). Except the sham operation group,the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia,all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase( SOD),glutathione( GSH),malondialdehyde( MDA) and lactic acid( LA) contents in brain tissue homogenate and the concentration of Ca~(2+),glutamate(Glu) and aspartate( Asp),creatine phosphate kinase( CK-BB) and lactate dehydrogenase( LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group,the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased,and the content of GSH and SOD was decreased; in cerebrospinal fluid,Ca~(2+)concentration was decreased,and the content of Glu and Asp,CK-BB and LDH increased significantly. As compared with the model group,the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity,reduce MDA and LA content in serum; increase Ca~(2+)concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats,and the mechanism may be related to recovering the blood brain barrier,scavenging free radicals,decreasing free Ca~(2+)inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.

关键词(KeyWords): 银杏二萜内酯葡胺注射液;脑缺血再灌注;超氧化物歧化酶;神经递质;钙离子
ginkgo diterpene lactone meglumine injection;cerebral ischemia reperfusion injury;super oxide dismutase;neurotransmitter;Ca2+

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2013ZX09402203);; 江苏省科技成果转化项目(BA2010109)

作者(Author): 罗燕平;张红;胡晗绯;曹泽彧;张新庄;曹亮;王振中;萧伟;
LUO Yan-ping;ZHANG Hong;HU Han-fei;CAO Ze-yu;ZHANG Xin-zhuang;CAO Liang;WANG Zhen-zhong;XIAO Wei;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Jiangsu Kanion Parmaceutical Co.,Ltd.;

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