高纯度银杏黄酮注射液对记忆功能及心肌组织超氧化物歧化酶的影响(英文)

Effects of high-purity ginkgetin injection on memory function and superoxide dismutase activity in myocardial tissues

背景:银杏黄酮的多种药用价值已被国内外认可,许多西方国家大量进口银杏叶提取物制成注射液出口,国内银杏叶产量大,但应用少,且没有注射制剂。目的:观察银杏黄酮注射液中总黄酮甙含量的提高和槲皮素甙含量的提高对小鼠记忆力、家兔缺血再灌注损伤心肌组织超氧化物歧化酶含量及家兔血液流变学的影响。设计:随机对照动物实验。单位:河北省职工医学院。材料:实验动物选择昆明种小白鼠(三四个月)90只。日本大耳白家兔(四五个月)32只。自制高纯度银杏黄酮注射液(5mL含银杏叶提取物17.5mg,其中银杏黄酮甙8.7mg,占提取物的49.8%,萜内酯4.61%);德国产银杏黄酮注射液(金纳多):德国威玛舒培大药房生产(标明物含5mL含银杏叶提取物17.5mg,其中银杏黄酮甙4.2mg,占24%)。方法:实验于2002-09/11在河北省职工医学院实验中心动物室完成。①将90只小鼠随机分为6组:自制银杏黄酮注射液1,2mL/kg组,德国产银杏黄酮注射液l,2mL/kg组,模型组和对照组,每组15只。各组分别腹腔注射所试药物,模型组和对照组采用生理盐水腹腔注射。连续10d。于第10天用药lh后,腹腔注射氢溴酸东莨菪碱2mL/kg,复制学习记忆障碍模型。10min后,将其置于跳台仪中,适应后给予36V电压刺激。训练5min,24h复测,记录触电潜伏期及5min内触电次数。②取日本大耳白家兔32只,随机分为正常对照组、德国产银杏黄酮注射液1mL/kg组、自制银杏黄酮注射液1.0,0.5mL/kg组,每组8只。耳缘静脉注射所试药物,3d后取血测血液流变学指标。③将32只家兔随机分为4组,自制银杏黄酮注射液组1,2mL/kg组,德国产银杏黄酮注射液2mL/kg组,生理盐水组,每组8只。制备家兔心肌缺血再灌注损伤模型,家兔冠状动脉结扎30min再松解方法造成心肌缺血灌注损伤,并于再灌注时即刻由颈动脉插管按不同组推注所试药物。于再灌注前分别注射所试药物,于再灌注前、再灌注30min、60min股动脉取血,测定血浆超氧化物歧化酶。处死动物后取心肌组织测定超氧化物歧化酶。主要观察指标:①记忆实验中触电潜伏期及5min内触电次数。②血液流变学指标和心肌组织超氧化物歧化酶含量侧定结果。结果:在实验过程中各组实验动物无死亡,全部进入结果分析。①记忆实验:自制银杏黄酮注射液组与德国产银杏黄酮注射液组跳台实验潜伏期和5min错误次数均明显好于对照组,差异具有显著性意义(P<0.01/0.05)。自制银杏黄酮注射液1mL/kg组5min错误次数少于同剂量德国产银杏黄酮注射液组,差异有显著性意义。②血流变学:自制银杏黄酮注射液1.0,0.5mL/kg组,德国产银杏黄酮注射液组1mL/kg组均可降低全血黏度低切值、红细胞刚性指数、红细胞压积等指标。③超氧化物歧化酶含量:自制银杏黄酮注射液1,2ml/kg与对照组比较均能明显提高缺血心肌超氧化物歧化酶含量,并呈剂量依赖关系。德国产银杏黄酮注射液1ml/kg组能明显提高缺血心肌超氧化物歧化酶含量,自制银杏黄酮注射液1mL/kg组较德国产银杏黄酮注射液2mL/kg组缺血心肌超氧化物歧化酶含量提高显著。结论:自制高纯度银杏黄酮注射液和德国产银杏黄酮注射液均能提高记忆力;且同剂量下自制高纯度银杏黄酮注射液作用优于德国产银杏黄酮注射液。

BACKGROUND： Ginkgetin has been widely acknowledged as having multiple pharmaceutical values in domestic and abroad. In many western countries, ginaton is imported in targe amount. Domestic production of ginkgetin is great, however, seldom applied and there is no ginaton agent for injection, OBJECTIVE： To observe the effects of the increased contents of total flavonoid glycoside and quercetin glycoside of ginkgetin injection on memory function of mice, superoxide dismutase （SOD） activity in myocardial tissues and hemorrheological indexes of rabbits with ischemia-reperfusion injury. DESIGN： Randomized control animal experiment. SETTING： Hebei Medical College of Employees. MATERIALS： Ninety Kunming mice （3-4 months old）, weight （25±1） g and thirty-two Japanese rabbits （3-4 months old） were selected, Self-made high-purity ginkgetin injection [5 mL containing 17.5 mg ginaton, of which there were 8.7 mg ginkgo flavonoid glycoside （49.8%） and 4.61% lactone]; Ginkgetin injection made in German （Jinnaduo）： Manufactured by Schwabe Germany [5 mL containing 17.5 mg ginaton, of which there were 4.2 mg ginkgo flavonoid glycoside （24%）]. METHODS： The experiment was conducted in the Central Department of Experimental Animal, Hebei Medical College of Employees from September to November 2002. ①Ninety mice were randomly divided into 6 groups： 1, 2 mL/kg self-made ginkgetin injection group, 1.2 mL/kg German ginkgetin injection group, model group and control group with 15 mice in each group. Mice in the model group and control group were intraperitoneally injected with normal saline, mice in each group were intraperitoneally injected respectively with testing medicine for 10 continuous days. One hour after the 10＇s day of administration, mice were intraperitoneally injected with 2 mL/kg scopolamine hydrobromide and dysnmesy models were duplicated. Ten minutes after that, mice were put in the step-down in- strument for 36V-voltage-stimulus after accommodation. Measurements were re-performed respectively at 5 minutes and 24 hours after training. Latency and times of electric shock within 5 minutes were recorded.②Thirty-two Japanese rabbits were selected and randomly divided into normal control group, Geromn ginkgetin injection group, 1 mL/kg, 0.5 mL/kg selfmade ginkgetin injection group with 8 rabbits in each group. Medicines were continuously injected into aural veins. Three days after administration, blood was collected to detect the hemorheological indexes. ③Thirtytwo rabbits were randomized into 4 groups： 1 mL/kg, 2 mL/kg self-made ginkgetin injection group, 2 mL/kg German ginkgetin injection group and normal saline group with 8 ones in each group, Rabbit models with ischemia-reperihsion injury in myoeardial tissues were established, rabbits were ligated for 30 minutes and then unclamped to get ischemic reperfusion injury in myocardial tissues, testing drugs were injected via carotid artery at the moment of reperfusion according to different groups. Before reperfusion and 30, 60 minutes after reperfusion, blood was drawn from the arteria femoralis, activity of SOD in plasma was measured. Animals were executed tO obtain myocardial tissues so as to measure SOD activity. MAIN OUTCOME MEASURES： ①Latency and times of shock within 5 minutes in the experiment were recorded.②Hemorheological indexes and determination of SOD activity in myocardial tissues. RESULTS： All experimental animals were involved in the analysis of resuits and no one died. ①Test for memory： Latency and times of errors in step down test in the injection group were better than those in the control group, and differences were significant （P 〈 0.01 or 0.05）. Times of errors within 5 minutes in 1 mL/kg self-made ginkgetln injection group was less than that in the German ginkgetin injection group and the differences were ohvious,②Hemorheological indexes; Whole-blood viscosity low shear value, rigid index of red cells and gathering index of red ceils etc. in injection groups decreased. ③SOD activity： Compared with control group, that was significantly increased in 1, 2 mL/kg self-made ginkgetin injection group and were in a dose-dependent manner. Those were obviously increased in the 1 mL/kg German ginkgetin injection group. Increase in SOD activity of ischemic myocardial tissues in the 1 mL/kg self-made ginkgetin injection group was more significant than that in the 2 mL/kg German ginkgetin injection group, CONCLUSION： Both self-made and German ginkgetin injections can enhance the ability of memory; While at the basis of same dose, self-made high-purity ginkgetin injection is superior to German ginkgetin injection.